Artículo

Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Connexinophaties are a collective of diseases related to connexin channels and hemichannels. In particular many Cx26 alterations are strongly associated to human deafness. Calcium plays an important role on this structures regulation. Here, using calcium as a probe, extensive atomistic Molecular Dynamics simulations were performed on the Cx26 hemichannel embedded in a lipid bilayer. Exploring different initial conditions and calcium concentration, simulation reached ∼4 μs. Several analysis were carried out in order to reveal the calcium distribution and localization, such as electron density profiles, density maps and distance time evolution, which is directly associated to the interaction energy. Specific amino acid interactions with calcium and their stability were capture within this context. Few of these sites such as, GLU42, GLU47, GLY45 and ASP50, were already suggested in the literature. Besides, we identified novel calcium biding sites: ASP2, ASP117, ASP159, GLU114, GLU119, GLU120 and VAL226. To the best of our knowledge, this is the first time that these sites are reported within this context. Furthermore, since various pathologies involving the Cx26 hemichannel are associated with pathogenic variants in the corresponding CJB2 gene, using ClinVar, we were able to spatially associate the 3D positions of the identified calcium binding sites within the framework of this work with reported pathogenic variants in the CJB2 gene. This study presents a first step on finding associations between molecular features and pathological variants of the Cx26 hemichannel. © 2018 Elsevier Ltd

Registro:

Documento: Artículo
Título:Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity
Autor:Albano, J.M.R.; Mussini, N.; Toriano, R.; Facelli, J.C.; Ferraro, M.B.; Pickholz, M.
Filiación:Facultad de Ciencias Exactas y Naturales, Departamento de Física, Universidad de Buenos Aires, Argentina
CONICET- Universidad de Buenos Aires, IFIBA, Buenos Aires, Argentina
Facultad de Medicina, Departamento de Ciencias Fisiológicas, Laboratorio de Biomembranas, Buenos Aires, Argentina
CONICET - Universidad de Buenos Aires, IFIBIO Houssay, Buenos Aires, Argentina
Department of Biomedical Informatics, The University of Utah, 421 Wakara Way, Suite 140, Salt Lake City, UT 84108, United States
Palabras clave:Connexin; Molecular dynamics; POPC; Variant annotation; Association reactions; Binding sites; Genes; Lipid bilayers; Molecular dynamics; Amino acid interactions; Atomistic molecular dynamics simulations; Calcium concentration; Calcium distributions; Connexin; Electron density profiles; POPC; Variant annotation; Calcium; calcium; DFNA3 protein, human; gap junction protein; binding site; chemistry; genetics; hearing impairment; human; lipid bilayer; metabolism; molecular dynamics; mutation; Binding Sites; Calcium; Connexins; Deafness; Humans; Lipid Bilayers; Molecular Dynamics Simulation; Mutation
Año:2018
Volumen:77
Página de inicio:331
Página de fin:342
DOI: http://dx.doi.org/10.1016/j.compbiolchem.2018.11.004
Título revista:Computational Biology and Chemistry
Título revista abreviado:Comput. Biol. Chem.
ISSN:14769271
CAS:calcium, 7440-70-2, 14092-94-5; Calcium; Connexins; DFNA3 protein, human; Lipid Bilayers
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14769271_v77_n_p331_Albano

Referencias:

  • Abraham, M.J., Murtola, T., Schulz, R., Páll, S., Smith, J.C., Hess, B., Gromacs: high performance molecular simulations through multi-level parallelism from laptops to supercomputers (2015) SoftwareX, 1-2, pp. 19-25. , PubMed PMID: 22713035
  • Albano, J.M.R., de Paula, E., Pickholz, M., (2018) Molecular Dynamics Simulations to Study Drug Delivery Systems, , A. Vakhrushev Molecular Dynamics IntechOpen
  • Ambrosi, C., Boassa, D., Pranskevich, J., Smock, A., Oshima, A., Xu, J., Analysis of four connexin26 mutant gap junctions and hemichannels reveals variations in hexamer stability (2010) Biophys. J., 98, pp. 1809-1819. , PubMed PMID: 20441744
  • Ambrosi, C., Boassa, D., Pranskevich, J., Smock, A., Oshima, A., Xu, J., Analysis of trafficking, stability and function of human connexin 26 gap junction channels … Supplemental Information (2013) PLoS One, 98
  • Araya-Secchi, R., Perez-Acle, T., Kang, S.G., Huynh, T., Bernardin, A., Escalona, Y., Characterization of a novel water pocket inside the human Cx26 hemichannel structure (2014) Biophys. J., 107, pp. 599-612. , PubMed PMID: 25099799
  • Bai-Lin Wu, P., Lindeman, N., Va, L., Effectiveness of sequencing connexin 26 (GJB2) in cases of familial or sporadic childhood deafness referred for molecular diagnostic testing (2002) Genet. Med., 4 (4), pp. 279-288. , 10.109700125817-200207000-00006 PubMed PMID: 12172394
  • Bajaj, Y., Sirimanna, T., Albert, D.M., Qadir, P., Jenkins, L., Bitner-Glindzicz, M., Spectrum of GJB2 mutations causing deafness in the British Bangladeshi population (2008) Clin. Otolaryngol., 33, pp. 313-318. , PubMed PMID: 18983339
  • Batool, A., Yasmeen, S., Rashid, S., T8M mutation in connexin-26 impairs the connexon topology and shifts its interaction paradigm with lipid bilayer leading to non-syndromic hearing loss (2017) J. Mol. Liq., 227 (100), pp. 168-177
  • Bavamian, S., Klee, P., Allagnat, F., Haefliger, J.A., Meda, P., Connexins and secretion (2009) Connexins: A Guide, pp. 511-527. , Humana Press Totowa, NJ
  • Beltramello, M., Piazza, V., Bukauskas, F.F., Pozzan, T., Mammano, F., Impaired permeability to Ins(1,4,5)P3 in a mutant connexin underlies recessive hereditary deafness (2005) Nat. Cell Biol., 7, pp. 63-69. , PubMed PMID: 15592461
  • Bennett, M.V.L., Contreras, J.E., Bukauskas, F.F., Sáez, J.C., New roles for astrocytes: gap junction hemichannels have something to communicate (2003) Trends Neurosci., 26, pp. 610-617. , PubMed PMID: 14585601
  • Bennett, B.C., Purdy, M.D., Baker, K.A., Acharya, C., McIntire, W.E., Stevens, R.C., An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels (2016) Nat. Commun., 7, p. 8770. , PubMed PMID: 26753910
  • Best, R.B., Zhu, X., Shim, J., Lopes, P.E.M., Mittal, J., Feig, M., Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone and side-chain and Dihedral Angles (2012) J. Chem. Theory Comput., 8, pp. 3257-3273. , PubMed PMID: 23341755
  • Beyer, E.C., Berthoud, V.M., Gap junction structure: unraveled, but not fully revealed (2017) F1000 Research, 6, p. 568. , PubMed PMID: 28529713
  • Bicego, M., Beltramello, M., Melchionda, S., Carella, M., Piazza, V., Zelante, L., Pathogenetic role of the deafness-related M34T mutation of Cx26 (2006) Hum. Mol. Genet., 15, pp. 2569-2587. , PubMed PMID: 16849369
  • Brobby, G.W., Muller-Myhsok, B., Connexin 26 R143W mutation associated with recessive nonsysndromic sensorineural deafness in Africa (1998) N. Engl. J. Med., 338, pp. 548-550
  • Bruzzone, R., Gomès, D., Denoyelle, E., Duval, N., Perea, J., Veronesi, V., Functional analysis of a dominant mutation of human connexin26 associated with nonsyndromic deafness (2001) Cell Commun. Adhes., 8, pp. 425-431. , PubMed PMID: 12064630
  • Bruzzone, R., Veronesi, V., Gomès, D., Bicego, M., Duval, N., Marlin, S., Loss-of-function and residual channel activity of connexin26 mutations associated with non-syndromic deafness (2003) FEBS Lett., 533, pp. 79-88. , PubMed PMID: 12505163
  • Capener, C.E., Sansom, M.S.P., Molecular dynamics simulations of a K channel model: sensitivity to changes in ions, waters, and membrane environment (2002) J. Phys. Chem. B, 106, pp. 4543-4551
  • Carrasquillo, M.M., Zlotogora, J., Barges, S., Chakravarti, A., Two different connexin 26 mutations in an inbred kindred segregating non-syndromic recessive deafness: implications for genetic studies in isolated populations (1997) Hum. Mol. Genet., 6, pp. 2163-2172. , PubMed PMID: 9328482
  • Chen, Y., Deng, Y., Bao, X., Reuss, L., Altenberg, G.A., Mechanism of the defect in gap-junctional communication by expression of a connexin 26 mutant associated with dominant deafness (2005) Faseb J., 19, pp. 1516-1518. , PubMed PMID: 16009703
  • Choi, S.-Y., Park, H.-J., Lee, K.Y., Dinh, E.H., Chang, Q., Ahmad, S., Different functional consequences of two missense mutations in the GJB2 gene associated with non-syndromic hearing loss (2009) Hum. Mutat., 30, pp. E716-E727. , PubMed PMID: 19384972
  • Choi, S.-Y., Lee, K.Y., H-KH-J, K., H-KH-J, K., Chang, Q., Park, H.-J., Functional evaluation of GJB2 variants in nonsyndromic hearing loss (2011) Mol. Med., 17, pp. 550-556. , PubMed PMID: 21298213
  • Cryns, K., Orzan, E., Murgia, A., Huygen, P.L.M., Moreno, F., del Castillo, I., A genotype-phenotype correlation for GJB2 (connexin 26) deafness (2004) J. Med. Genet., 41, pp. 147-154. , PubMed PMID: 14985372
  • Da, G., DeRosa, A.M., Richard, G., White, T.W., Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness (2007) Am. J. Physiol. Cell Physiol., 293, pp. C337-C345. , PubMed PMID: 17428836
  • Delmar, M., Makita, N., Cardiac connexins, mutations and arrhythmias (2012) Curr. Opin. Cardiol., 27, pp. 236-241. , PubMed PMID: 22382502
  • Ea, D.Z.-S., van Geel, M., van Neer, P.F., Steijlen, P.M., Martin, P.E., van Steensel, M.M., A novel missense mutation in the second extracellular domain of GJB2, p.Ser183Phe, causes a syndrome of focal palmoplantar keratoderma with deafness (2008) Am. J. Pathol., 173, pp. 1113-1119. , PubMed PMID: 18787097
  • Elias, L.A., Wang, D.D., Kriegstein, A.R., Gap junction adhesion is necessary for radial migration in the neocortex (2007) Nature, 448, pp. 901-907. , PubMed PMID: 17713529
  • Evans, W.H., Martin, P.E.M., Gap junctions: structure and function (Review) (2002) Mol. Membr. Biol., 19, pp. 121-136. , PubMed PMID: 12126230
  • Ewald, P.P., Die berechnung optischer und elektrostatisher gitterpotentiale (1921) Ann. Phys., 64, pp. 253-287
  • Figueroa, X.F., Duling, B.R., Gap junctions in the control of vascular function (2009) Antioxid. Redox Signal., 11, pp. 251-266. , PubMed PMID: 18831678
  • García, I.E., Maripillán, J., Jara, O., Ceriani, R., Palacios-Muñoz, A., Ramachandran, J., Keratitis-ichthyosis-deafness syndrome-associated Cx26 mutants produce nonfunctional gap junctions but hyperactive hemichannels when Co-expressed with wild type Cx43 (2015) J. Invest. Dermatol., 135, pp. 1338-1347. , PubMed PMID: 25625422
  • García, I.E., Prado, P., Pupo, A., Jara, O., Rojas-Gómez, D., Mujica, P., Connexinopathies: a structural and functional glimpse (2016) BMC Cell Biol., 17, p. S17. , PubMed PMID: 27228968
  • García-Jaramillo, M., Calm, R., Bondia, J., Tarín, C., Vehí, J., Insulin dosage optimization based on prediction of postprandial glucose excursions under uncertain parameters and food intake (2012) Comput. Methods Programs Biomed., 105, pp. 61-69
  • González, D., Gómez-Hernández, J.M., Barrio, L.C., Species specificity of mammalian connexin-26 to form open voltage-gated hemichannels (2006) Faseb J., 20, pp. 2329-2338. , PubMed PMID: 17077310
  • Gualandi, F., Ravani, A., Berto, A., Sensi, A., Trabanelli, C., Falciano, F., Exploring the clinical and epidemiological complexity of GJB2 -Linked deafness (2002) Am. J. Med. Genet., 45, pp. 38-45
  • Ha, S., Mese, G., Srinivas, M., White, T.W., Verselis, V.K., Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome (2010) J. Gen. Physiol., 136, pp. 47-62. , PubMed PMID: 20584891
  • Hamelmann, C., Amedofu, G., Albrecht, K., Muntau, B., Gelhaus, A., Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana (2001) Hum. Mutat., 18 (84Á85). , 18:84-5
  • Han, S.H., Park, H.J., Kang, E.J., Ryu, J.S., Lee, A., Yang, Y.H., Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population (2008) J. Hum. Genet., 53, pp. 1022-1028. , PubMed PMID: 19043807
  • Hanner, F., Sorensen, C.M., Holstein-Rathlou, N.-H., Peti-Peterdi, J., Connexins and the kidney (2010) Am. J. Physiol. Regul. Integr. Comp. Physiol., 298, pp. R1143-55. , PubMed PMID: 20164205
  • Heathcote, K., Syrris, P., Carter, N.D., Patton, M., A connexin 26 mutation causes a syndrome of sensorineural hearing loss and palmoplantar hyperkeratosis (MIM 148350) (2000) J. Med. Genet., 37, pp. 50-51. , PubMed PMID: 10633135
  • Herce, H.D., Garcia, A.E., Darden, T., The electrostatic surface term:(I) periodic systems (2007) J. Chem. Phys., 126
  • Hess, B., Kutzner, C., van der Spoel, D., Lindahl, E., GROMACS 4: algorithms for highly efficient, load balanced, and scalable molecular simulations (2008) J. Chem. Theory Comput., 4, pp. 435-447
  • Hoover, W.G., Canonical dynamics: equilibrium phase-space distributions (1985) Phys. Rev., 31, pp. 1695-1697. , PubMed PMID: 9895674
  • Humphrey, W., Dalke, A., Schulten, K., VMD: visual molecular dynamics (1996) J. Mol. Graph., 14, pp. 33-38. , PubMed PMID: 8744570
  • Hung, A., Yarovsky, I., Gap junction hemichannel interactions with zwitterionic lipid, anionic lipid, and cholesterol: molecular simulation studies (2011) Biochemistry, 50, pp. 1492-1504. , PubMed PMID: 21241055
  • Iossa, S., Marciano, E., Franzé, A., GJB2 gene mutations in syndromic skin diseases with sensorineural hearing loss (2011) Curr. Genomics, 12, pp. 475-785. , PubMed PMID: 22547955
  • Jo, S., Kim, T., Iyer, V., Im, W., CHARMM GUI: a web based graphical user interface for CHARMM (2008) J. Comput. Chem., 29, pp. 1859-1865
  • Jones, D.E., Lund, A.M., Ghandehari, H., Facelli, J.C., Molecular dynamics simulations in drug delivery research: calcium chelation of G3.5 PAMAM dendrimers (2016) Cogent Chem., 2
  • Kabsch, W., A solution for the best rotation to relate two sets of vectors (1976) Acta Crystallogr. Sect. A, 32, pp. 922-923. , PubMed PMID: 96
  • Kelsell, D.P., Di W-L, H.M.J., Connexin mutations in skin disease and hearing loss (2001) Am. J. Hum. Genet., 68, pp. 559-568. , PubMed PMID: 11179004
  • Kelsell, D.P., Dunlop, J., Stevens, H.P., Lench, N.J., Liang, J.N., Parry, G., Connexin 26 mutations in hereditary non-syndromic sensorineural deafness (1997) Nature, 387, pp. 80-83. , PubMed PMID: 9139825
  • Kenna, M.A., Wu, B.L., Cotanche, D.A., Korf, B.R., Rehm, H.L., Connexin 26 studies in patients with sensorineural hearing loss (2001) Arch. Otolaryngol. Head Neck Surg., 127, pp. 1037-1042. , PubMed PMID: 11556849
  • Kwon, T., Roux, B., Jo, S., Klauda, J.B., Harris, A.L., Bargiello, T.A., Molecular dynamics simulations of the Cx26 hemichannel: insights into voltage-dependent loop-gating (2012) Biophys. J., 102, pp. 1341-1351. , PubMed PMID: 22455917
  • Kyle, J.W., Minogue, P.J., Thomas, B.C., DaL, D., Berthoud, V.M., Da, H., An intact connexin N-terminus is required for function but not gap junction formation (2008) J. Cell. Sci., 121, pp. 2744-2750. , PubMed PMID: 18664489
  • Landrum, M.J., Lee, J.M., Riley, G.R., Jang, W., Rubinstein, W.S., Church, D.M., ClinVar: public archive of relationships among sequence variation and human phenotype (2014) Nucleic Acids Res., 42, pp. D980-D985. , PubMed PMID: 24234437
  • Lee, J.R., Derosa, A.M., White, T.W., Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes (2009) J. Invest. Dermatol., 129, pp. 870-878. , PubMed PMID: 18987669
  • Locke, D., Koreen, I.V., Harris, A.L., Isoelectric points and post-translational modifications of connexin26 and connexin32 (2006) Faseb J., 20, pp. 1221-1223. , PubMed PMID: 16645047
  • Löffler, J., Nekahm, D., Hirst-Stadlmann, A., Günther, B., Menzel, H.J., Utermann, G., Sensorineural hearing loss and the incidence of Cx26 mutations in Austria (2001) Eur. J. Hum. Genet., 9, pp. 226-230. , PubMed PMID: 11313763
  • Lopez, W., Gonzalez, J., Liu, Y., Harris, A.L., Contreras, J.E., Insights on the mechanisms of Ca(2+) regulation of connexin26 hemichannels revealed by human pathogenic mutations (D50N/Y) (2013) J. Gen. Physiol., 142, pp. 23-35. , PubMed PMID: 23797420
  • Lopez, W., Ramachandran, J., Alsamarah, A., Luo, Y., Harris, A.L., Contreras, J.E., Mechanism of gating by calcium in connexin hemichannels (2016) Proc. Natl. Acad. Sci.
  • Mab, V., Ta, V., Pa, P., Sa, S., Ta, H., Rogiers, V., Connexins and their channels in cell growth and cell death (2006) Cell. Signal., 18, pp. 592-600
  • Maeda, S., Tsukihara, T., Structure of the gap junction channel and its implications for its biological functions (2011) Cell. Mol. Life Sci., 68, pp. 1115-1129
  • Maeda, S., Nakagawa, S., Suga, M., Yamashita, E., Oshima, A., Fujiyoshi, Y., Structure of the connexin 26 gap junction channel at 3.5 A resolution (2009) Nature, 458, pp. 597-602. , PubMed PMID: 19340074
  • Mahoney, M.W., Jorgensen, W.L., A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions (2000) J. Chem. Phys., 112, p. 8910. , PubMed PMID: 86851200022
  • Man, Y.K.S., Trolove, C., Tattersall, D., Thomas, A.C., Papakonstantinopoulou, A., Patel, D., A deafness-associated mutant human connexin 26 improves the epithelial barrier in vitro (2007) J. Membr. Biol., 218, pp. 29-37. , PubMed PMID: 17581693
  • Mani, R.S., Ganapathy, A., Jalvi, R., Srikumari Srisailapathy, C.R., Malhotra, V., Chadha, S., Functional consequences of novel connexin 26 mutations associated with hereditary hearing loss (2009) Eur. J. Hum. Genet., 17, pp. 502-509. , PubMed PMID: 18941476
  • Marlin, S., Garabédian, E.N., Roger, G., Moatti, L., Matha, N., Lewin, P., Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling (2001) Arch. Otolaryngol. Head Neck Surg., 127, pp. 927-933. , PubMed PMID: 11493200
  • Martin, P.E.M., Coleman, S.L., Casalotti, S.O., Forge, A., Howard Evans, W., Properties of Connexin26 gap junctional proteins derived from mutations associated with non-syndromal heriditary deafness (1999) Hum. Mol. Genet., 8, pp. 2369-2376. , PubMed PMID: 10556284
  • Marziano, N.K., Casalotti, S.O., Portelli, A.E., Becker, D.L., Forge, A., Mutations in the gene for connexin 26 (GJB2) that cause hearing loss have a dominant negative effect on connexin 30 (2003) Hum. Mol. Genet., 12, pp. 805-812. , PubMed PMID: 12668604
  • Meigh, L., Hussain, N., Mulkey, D.K., Dale, N., Connexin26 hemichannels with a mutation that causes KID syndrome in humans lack sensitivity to CO2 (2014) eLife, 3. , PubMed PMID: 25422938
  • Meşe, G., Londin, E., Mui, R., Brink, P.R., White, T.W., Altered gating properties of functional Cx26 mutants associated with recessive non-syndromic hearing loss (2004) Hum. Genet., 115, pp. 191-199. , PubMed PMID: 15241677
  • Meşe, G., Valiunas, V., Brink, P.R., White, T.W., Connexin26 deafness associated mutations show altered permeability to large cationic molecules (2008) Am. J. Physiol. Cell Physiol., 295, pp. C966-74. , PubMed PMID: 18684989
  • Mhaske, P.V., Na, L., Li, L., Wang, H.-Z., Lee, J.R., Shuja, Z., The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity (2013) Am. J. Physiol. Cell Physiol., 304, pp. C1150-8. , PubMed PMID: 23447037
  • Nemoto-Hasebe, I., Akiyama, M., Yamada, N., Inoue, Y., Touge, C., Shimizu, H., Keratitis-ichthyosis-deafness syndrome lacking subjective hearing impairment (2008) Acta Derm. Venereol., 88, pp. 406-408. , PubMed PMID: 18709320
  • Nielsen, M.S., Axelsen, L.N., Sorgen, P.L., Verma, V., Delmar, M., Holstein-Rathlou, N.-H., Gap junctions (2012) Compr. Physiol., 2, pp. 1981-2035. , PubMed PMID: 23723031
  • Nosé, S., A unified formulation of the constant temperature molecular dynamics methods (1984) J. Chem. Phys., 81, p. 511
  • Ogawa, Y., Takeichi, T., Kono, M., Hamajima, N., Yamamoto, T., Sugiura, K., Revertant mutation releases confined lethal mutation, opening Pandora's Box: a novel genetic pathogenesis (2014) PLoS Genet., 10. , PubMed PMID: 24785414
  • Oguchi, T., Ohtsuka, A., Hashimoto, S., Oshima, A., Abe, S., Kobayashi, Y., Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns (2005) J. Hum. Genet., 50, pp. 76-83. , PubMed PMID: 15700112
  • Oshima, A., Structure and closure of connexin gap junction channels (2014) FEBS Lett., 588, pp. 1230-1237. , PubMed PMID: 24492007
  • Palmada, M., Schmalisch, K., Böhmer, C., Schug, N., Pfister, M., Lang, F., Loss of function mutations of the GJB2 gene detected in patients with DFNB1-associated hearing impairment (2006) Neurobiol. Dis., 22, pp. 112-118. , PubMed PMID: 16300957
  • Pantano, S., Zonta, F., Mammano, F., A fully atomistic model of the Cx32 connexon (2008) PLoS One, 3, pp. 1-11. , PubMed PMID: 18648547
  • Parrinello, M., Rahman, A., Strain fluctuations and elastic constants (1982) J. Chem. Phys., 76, pp. 2662-2666. , PubMed PMID: 25246403
  • Pasenkiewicz-Gierula, M., Takaoka, Y., Miyagawa, H., Kitamura, K., Kusumi, A., Charge pairing of headgroups in phosphatidylcholine membranes: a molecular dynamics simulation study (1999) Biophys. J., 76, pp. 1228-1240. , PubMed PMID: 10049307
  • Peracchia, C., Chemical gating of gap junction channels: roles of calcium, pH and calmodulin (2004) Biochim. Biophys. Acta Biomembr., 1662, pp. 61-80. , PubMed PMID: 15033579
  • Pettersen, E.F., Goddard, T.D., Huang, C.C., Couch, G.S., Greenblatt, D.M., Meng, E.C., UCSF Chimera–a visualization system for exploratory research and analysis (2004) J. Comput. Chem., 25 (13), pp. 1605-1612. , Epub 2004/07/21 PubMed PMID: 15264254
  • Pickholz, M., Fernandes Fraceto, L., de Paula, E., Distribution of neutral prilocaine in a phospholipid bilayer: insights from molecular dynamics simulations (2008) Int. J. Quantum Chem., 108, pp. 2386-2391
  • Posukh, O., Pallares-Ruiz, N., Tadinova, V., Osipova, L., Claustres, M., Roux, A.-F., First molecular screening of deafness in the Altai Republic population (2005) BMC Med. Genet., 6, p. 12. , PubMed PMID: 15790391
  • Pravda, L., Sehnal, D., Tousek, D., Navratilova, V., Bazgier, V., Berka, K., MOLEonline: a web-based tool for analyzing channels, tunnels and pores (2018 update) (2018) Nucleic Acids Res., 46 (W1), pp. W368-w373. , Epub 2018/05/03, PubMed PMID: 29718451; PubMed Central PMCID: PMCPMC6030847
  • Primignani, P., Castorina, P., Sironi, F., Curcio, C., Ambrosetti, U., Coviello, D.A., A novel dominant missense mutation–D179N–in the GJB2 gene (Connexin 26) associated with non-syndromic hearing loss (2003) Clin. Genet., 63, pp. 516-521. , 079 [pii]. PubMed PMID: 12786758
  • Rouan, F., White, T.W., Brown, N., aM, T., Lucke, T.W., Paul, D.L., Trans-dominant inhibition of Connexin-43 by mutant Connexin-26: implications for dominant connexin disorders affecting epidermal differentiation (2001) J. Cell. Sci., 114, pp. 2105-2113. , PubMed PMID: 11493646
  • Sanchez, H.A., Verselis, V.K., Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: insights into syndromic hearing loss (2014) Front. Cell. Neurosci., 8, p. 354. , PubMed PMID: 25386120
  • Santos, R.L.P., Wajid, M., Pham, T.L., Hussan, J., Ali, G., Ahmad, W., Low prevalence of Connexin 26 (GJB2) variants in Pakistani families with autosomal recessive non-syndromic hearing impairment (2005) Clin. Genet., 67, pp. 61-68. , PubMed PMID: 15617550
  • Scott, C.A., Tattersall, D., O'Toole, E.A., Kelsell, D.P., Connexins in epidermal homeostasis and skin disease (2012) Biochim. Biophys. Acta Biomembr., 1818, pp. 1952-1961. , PubMed PMID: 21933662
  • Snoeckx, R.L., Huygen, P.L., Feldmann, D., Marlin, S., Denoyelle, F., Waligora, J., GJB2 mutations and degree of hearing loss: a multicenter study (2005) Am. J. Hum. Genet., 77, pp. 945-957. , PubMed PMID: 16380907
  • Srinivas, M., Verselis, V.K., White, T.W., Human diseases associated with connexin mutations (2017) Biochim. Biophys. Acta (BBA) – Biomembr., , PubMed PMID: 28457858
  • Stong, B.C., Chang, Q., Ahmad, S., Lin, X., A novel mechanism for connexin 26 mutation linked deafness: cell death caused by leaky gap junction hemichannels (2006) Laryngoscope, 116, pp. 2205-2210. , PubMed PMID: 17146396
  • Su, C.-C., Li, S.-Y., Su, M.-C., Chen, W.-C., Yang, J.-J., Mutation R184Q of connexin 26 in hearing loss patients has a dominant-negative effect on connexin 26 and connexin 30 (2010) Eur. J. Hum. Genet., 18, pp. 1061-1064. , PubMed PMID: 20442751
  • Tekin, M., Arnos, K.S., Xia, X.J., Oelrich, M.K., Liu, X.Z., Nance, W.E., W44C mutation in the connexin 26 gene associated with dominant non-syndromic deafness (2001) Clin. Genet., 59, pp. 269-273. , PubMed PMID: 11298683
  • Thönnissen, E., Rabionet, R., Arbonès, M.L., Estivill, X., Willecke, K., Ott, T., Human connexin26 (GJB2) deafness mutations affect the function of gap junction channels at different levels of protein expresion (2002) Hum. Genet., 111, pp. 190-197. , PubMed PMID: 12189493
  • Tóth, T., Kupka, S., Haack, B., Riemann, K., Braun, S., Fazakas, F., GJB2 mutations in patients with non-syndromic hearing loss from Northeastern Hungary (2004) Hum. Mutat., 23, pp. 631-632. , PubMed PMID: 15146474
  • Trosko, J.E., Ruch, R.J., Cell-cell communication in carcinogenesis (1998) Front Biosci., 3, pp. d208-36. , PubMed PMID: 9458335
  • Vendome, J., Posy, S., Jin, X., Bahna, F., Ahlsen, G., Shapiro, L., Molecular design principles underlying β-strand swapping in the adhesive dimerization of cadherins (2011) Nat. Struct. Mol. Biol., 18, pp. 693-700. , PubMed PMID: 1000000221
  • Villanelo, F., Escalona, Y., Pareja-Barrueto, C., Garate, J.A., Skerrett, I.M., Perez-Acle, T., Accessing gap-junction channel structure-function relationships through molecular modeling and simulations (2017) BMC Cell Biol., 18, p. 5
  • Vinken, M., Introduction: connexins, pannexins and their channels as gatekeepers of organ physiology (2015) Cell. Mol. Life Sci., 72, pp. 2775-2778
  • Wang, H.L., Chang, W.T., Li, A.H., Yeh, T.H., Wu, C.Y., Chen, M.S., Functional analysis of connexin-26 mutants associated with hereditary recessive deafness (2003) J. Neurochem., 84, pp. 735-742. , PubMed PMID: 12562518
  • Wen, J., Scoles, D.R., Facelli, J.C., Effects of the enlargement of polyglutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins (2017) J. Biomol. Struct. Dyn., 35, pp. 504-519. , PubMed PMID: 26861241
  • Wu, Y., Tepper, H.L., Voth, G.A., Flexible simple point-charge water model with improved liquid-state properties (2006) J. Chem. Phys., 124. , PubMed PMID: 16422607
  • Wu, E.L., Cheng, X., Jo, S., Rui, H., Song, K.C., Dávila-Contreras, E.M., CHARMM-GUI Membrane Builder toward realistic biological membrane simulations (2014) J. Comput. Chem., 35, pp. 1997-2004
  • Yeager, M., Harris, A.L., Gap junction channel structure in the early 21st century: facts and fantasies (2007) Curr. Opin. Cell Biol., 19, pp. 521-528. , PubMed PMID: 17945477
  • Yong-Yi, Y., Pu, D., Fei, Y., Xiu-Hui, Z., Hui-Jun, Y., Dong-Yi, H., GJB2 mutation spectrum in Inner Mongolia and its comparison with other Asian populations (2007) J. Otol., 2, pp. 81-91
  • Yum, S.W., Zhang, J., Scherer, S.S., Dominant connexin26 mutants associated with human hearing loss have trans-dominant effects on connexin30 (2010) Neurobiol. Dis., 38, pp. 226-236. , PubMed PMID: 20096356
  • Zhang, Y., Tang, W., Ahmad, S., Ja, S., Chen, P., Lin, X., Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions (2005) Proc. Natl. Acad. Sci. U. S. A., 102, pp. 15201-15206. , PubMed PMID: 16217030
  • Zhang, J., Scherer, S.S., Yum, S.W., Dominant Cx26 mutants associated with hearing loss have dominant-negative effects on wild type Cx26 (2011) Mol. Cell. Neurosci., 47, pp. 71-78. , PubMed PMID: 21040787
  • Zheng, J., Ying, Z., Cai, Z., Sun, D., He, Z., Gao, Y., GJB2 mutation spectrum and genotype-phenotype correlation in 1067 Han Chinese subjects with non-syndromic hearing loss (2015) PLoS One, (10). , PubMed PMID: 26043044
  • Zonta, F., Polles, G., Zanotti, G., Mammano, F., Permeation pathway of homomeric connexin 26 and connexin 30 channels investigated by molecular dynamics (2012) J. Biomol. Struct. Dyn., 29, pp. 985-998. , PubMed PMID: 22292956
  • Zonta, F., Polles, G., Zanotti, G., Mammano, F., Permeation pathway of homomeric connexin 26 and connexin 30 channels investigated by molecular dynamics (2012) J. Biomol. Struct. Dyn., 29 (5), pp. 985-998
  • Zonta, F., Buratto, D., Cassini, C., Bortolozzi, M., Mammano, F., Molecular dynamics simulations highlight structural and functional alterations in deafness-related M34T mutation of connexin 26 (2014) Front. Physiol., 5 (March), pp. 1-9. , PubMed PMID: 24624091
  • Zonta, F., Mammano, F., Torsello, M., Fortunati, N., Orian, L., Polimeno, A., Role of gamma carboxylated Glu47 in connexin 26 hemichannel regulation by extracellular Ca²+: insight from a local quantum chemistry study (2014) Biochem. Biophys. Res. Commun., 445, pp. 10-15. , PubMed PMID: 24468086

Citas:

---------- APA ----------
Albano, J.M.R., Mussini, N., Toriano, R., Facelli, J.C., Ferraro, M.B. & Pickholz, M. (2018) . Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity. Computational Biology and Chemistry, 77, 331-342.
http://dx.doi.org/10.1016/j.compbiolchem.2018.11.004
---------- CHICAGO ----------
Albano, J.M.R., Mussini, N., Toriano, R., Facelli, J.C., Ferraro, M.B., Pickholz, M. "Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity" . Computational Biology and Chemistry 77 (2018) : 331-342.
http://dx.doi.org/10.1016/j.compbiolchem.2018.11.004
---------- MLA ----------
Albano, J.M.R., Mussini, N., Toriano, R., Facelli, J.C., Ferraro, M.B., Pickholz, M. "Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity" . Computational Biology and Chemistry, vol. 77, 2018, pp. 331-342.
http://dx.doi.org/10.1016/j.compbiolchem.2018.11.004
---------- VANCOUVER ----------
Albano, J.M.R., Mussini, N., Toriano, R., Facelli, J.C., Ferraro, M.B., Pickholz, M. Calcium interactions with Cx26 hemmichannel: Spatial association between MD simulations biding sites and variant pathogenicity. Comput. Biol. Chem. 2018;77:331-342.
http://dx.doi.org/10.1016/j.compbiolchem.2018.11.004