Simulation of gap junction formation reveals critical role of Cys disulfide redox state in connexin hemichannel docking
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Harris AL. Connexin channel permeability to cytoplasmic molecules. Prog Biophys Mol Biol. 200794. https://doi.org/10.1016/j.pbiomolbio.2007.03.011.
Kotini M, et al. Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo. Nat Commun. 2018;9:3846.
Martin PE, Kwak BR. An overview of the focus of the international gap junction conference 2017 and future perspectives. Int J Mol Sci. 2018;19:2823. https://doi.org/10.3390/ijms19092823.
Valiunas V, Cohen IS, Brink PR. Defining the factors that affect solute permeation of gap junction channels. Biochim Biophys Acta Biomembr. 2018;1860:96–101. https://doi.org/10.1016/j.bbamem.2017.07.002.
Ambrosi C, et al. Analysis of trafficking, stability and function of human Connexin 26 gap junction channels with deafness-causing mutations in the fourth transmembrane helix. PLoS One. 2013;8:e70916.
Ambrosi C, et al. Connexin43 forms supramolecular complexes through non-overlapping binding sites for drebrin, tubulin, and ZO-1. PLoS One. 2016;11:e0157073.
Bargiello TA, et al. Gating of Connexin Channels by transjunctional-voltage: Conformations and models of open and closed states. Biochim Biophys Acta Biomembr. 2018;1860:22–39.
Batir Y, Bargiello TA, Dowd TL. Structural studies of N-terminal mutants of Connexin 26 and Connexin 32 using 1H NMR spectroscopy. Arch Biochem Biophys. 2016;608:8–19.
Bennett BC, et al. An electrostatic mechanism for Ca 2+ -mediated regulation of gap junction channels. Nat Commun. 2016;7:1–12.
Bevans CG, Harris AL. Regulation of connexin channels by pH: Direct action of the protonated form of taurine and other aminosulfonates. J Biol Chem. 1999;274:3711–9.
Beyer EC, Lipkind GM, Kyle JW, Berthoud VM. Structural organization of intercellular channels II. Amino terminal domain of the connexins: Sequence, functional roles, and structure. Biochim Biophys Acta Biomembr. 2012;1818. https://doi.org/10.1016/j.bbamem.2011.10.011.
Chen VC, Gouw JW, Naus CC & Foster LJ. Connexin multi-site phosphorylation: Mass spectrometry-based proteomics fills the gap. Biochim Biophys Acta Biomembr. 2013;1828. https://doi.org/10.1016/j.bbamem.2012.02.028.
EkVitorín JF, Pontifex TK, Burt JM. Determinants of Cx43 Channel Gating and Permeation: The Amino Terminus. Biophys J. 2016;110:127–40.
Fernández-Olivares A, et al. Extracellular cysteines are critical to form functional Cx46 hemichannels. Int J Mol Sci. 2022;23:7252.
Flores CE, et al. Trafficking of gap junction channels at a vertebrate electrical synapse in vivo. Proc Natl Acad Sci U S A. 2012;109:E573-82.
Gaietta G, et al. Multicolor and electron microscopic imaging of connexin trafficking. Science (80- ). 2002;296:503–7.
Lopez W, et al. Mechanism of gating by calcium in connexin hemichannels. Proc Natl Acad Sci U S A. 2016;113:E7986–95.
Moreno AP. Connexin phosphorylation as a regulatory event linked to channel gating. Biochim Biophys Acta Biomembr. 2005;1711. https://doi.org/10.1016/j.bbamem.2005.02.016.
Myers JB, et al. Structure of native lens connexin 46/50 intercellular channels by cryo-EM. Nature. 2018;564:372–7.
Oh S, Bargiello TA. Voltage regulation of connexin channel conductance. Yonsei Med J. 2015;56:1–5.
Raškevičius V, et al. Molecular basis for potentiation of Cx36 gap junction channel conductance by n-alcohols and general anesthetics. Biosci Rep. 2018;38:BSR20171323.
Oshima A. Structure and closure of connexin gap junction channels. FEBS Letters. 2014;588:1230–7.
Pogoda K, Kameritsch P, Retamal MA & Vega JL. Regulation of gap junction channels and hemichannels by phosphorylation and redox changes: A revision. BMC Cell Biol. 2016;17. https://doi.org/10.1186/s12860-016-0099-3.
Sánchez A, Castro C, Flores DL, Gutiérrez E & Baldi P. Gap junction channels of innexins and connexins: Relations and computational perspectives. Int J Mol Sci. 2019;20 . https://doi.org/10.3390/ijms20102476.
Stout RF, Spray DC. Cysteine residues in the cytoplasmic carboxy terminus of connexins dictate gap junction plaque stability. Mol Biol Cell. 2017;28:2757–64.
Su V, Lau AF. Connexins: Mechanisms regulating protein levels and intercellular communication. FEBS Letters. 2014;588:1212–20.
Unwin PNT, Ennis PD. Calcium-mediated changes in gap junction structure: Evidence from the low angle x-ray pattern. J Cell Biol. 1983;97:1459–66.
Verselis VK, Trelles MP, Rubinos C, Bargiello TA, Srinivas M. Loop gating of connexin hemichannels involves movement of pore-lining residues in the first extracellular loop domain. J Biol Chem. 2009;284:4484–93.
Thévenin AF. et al. Proteins and mechanisms regulating gap-junction assembly, internalization, and degradation. Physiol. 2013;28. https://doi.org/10.1152/physiol.00038.2012.
Unger VM, Kumar NM, Gilula NB, Yeager M. Three-dimensional structure of a recombinant gap junction membrane channel. Science (80- ). 1999;283:1176–80.
Beyer EC & Berthoud VM. Gap junction structure: Unraveled, but not fully revealed. F1000Res. 2017;6. https://doi.org/10.12688/f1000research.10490.1.
Dahl G, Levine E, Rabadan-Diehl C, Werner R. Cell/cell channel formation involves disulfide exchange. Eur J Biochem. 1991;197:141–4.
Dahl G, Werner R, Levine E, Rabadan-Diehl C. Mutational analysis of gap junction formation. Biophys J. 1992;62:172–82.
Dupont E, El Aoumari A, Briand JP, Fromaget C, Gross D. Cross-linking of cardiac gap junction connexons by thiol/disulfide exchanges. J Membr Biol. 1989;108:247–52.
Foote CI, Zhou L, Zhu X, Nicholson BJ. The pattern of disulfide linkages in the extracellular loop regions of connexin 32 suggests a model for the docking interface of gap junctions. J Cell Biol. 1998;140:1187–97.
John SA, Revel JP. Connexon integrity is maintained by non-covalent bonds: intramolecular disulfide bonds link the extracellular domains in rat connexin-43. Biochem Biophys Res Commun. 1991;178:1312–8.
Rahman S, Howard Evans W. Topography of connexin32 in rat liver gap junctions: Evidence for an intramolecular disulphide linkage connecting the two extracellular peptide loops. J Cell Sci. 1991;100:567–78.
García I E, Sánchez HA, Martínez AD & Retamal MA. Redox-mediated regulation of connexin proteins; focus on nitric oxide. Biochim Biophys Acta Biomembr. 2018;1860. https://doi.org/10.1016/j.bbamem.2017.10.006.
Retamal MA, et al. Extracellular cysteine in connexins: Role as redox sensors. Front Physiol. 2016;7:1.
Aasen T, Johnstone S, Vidal-Brime L, Lynn KS & Koval M. Connexins: Synthesis, post-translational modifications, and trafficking in health and disease. Int J Mol Sci. 2018;19. https://doi.org/10.3390/ijms19051296.
Bai D, Yue B, Aoyama H. Crucial motifs and residues in the extracellular loops influence the formation and specificity of connexin docking. Biochim Biophys Acta Biomembr. 2018. https://doi.org/10.1016/j.bbamem.2017.07.003.
Beyer EC, Berthoud VM. The family of connexin genes. Connexins: A Guide 3–26 (Humana Press Inc., 2009). https://link.springer.com/chapter/10.1007/978-1-59745-489-6_1#citeas.
Delvaeye T, Vandenabeele P, Bultynck G, Leybaert L & Krysko DV. Therapeutic Targeting of Connexin Channels: New Views and Challenges. Trends Mol Med. 2018;24 1036–1053. https://doi.org/10.1016/j.molmed.2018.10.005.
Denoyelle F et al. Connexin 26 gene linked to a dominant deafness [9]. Nature. 1998;393. https://doi.org/10.1038/30639.
Beyer EC, Ebihara L & Berthoud VM. Connexin mutants and cataracts. Front Pharmacol. 2013;4 APR. https://doi.org/10.3389/fphar.2013.00043.
Laird DW, Lampe PD. Therapeutic strategies targeting connexins. Nat Rev Drug Discov. 2018;17:905–21. https://doi.org/10.1038/nrd.2018.138.
Leybaert L, et al. Connexins in cardiovascular and neurovascular health and disease: Pharmacological implications. Pharmacol Rev. 2017;69:396–478.
Nagy JI, Pereda AE & Rash JE. Electrical synapses in mammalian CNS: Past eras, present focus and future directions. Biochim Biophys Acta Biomembr. 2018;1860. https://doi.org/10.1016/j.bbamem.2017.05.019.
Nielsen MS, et al. Gap junctions. Compr Physiol. 2012;2:1981–2035.
Hoorelbeke D, et al. Cx43 channels and signaling via IP3/Ca2+, ATP, and ROS/NO propagate radiation-induced DNA damage to non-irradiated brain microvascular endothelial cells. Cell Death Dis. 2020;11:194.
Xiao S, et al. Auxiliary trafficking subunit GJA1–20k protects connexin-43 from degradation and limits ventricular arrhythmias. J Clin Invest. 2020;130:4858–70.
Willecke K. et al. Structural and functional diversity of connexin genes in the mouse and human genome. Biolo Chemi. 2002;383. https://doi.org/10.1515/BC.2002.076
Winterhager E. Gap junctions in development and disease. Gap Junctions in Development and Disease. 2005. https://doi.org/10.1007/3-540-28621-7.
Vincze R, et al. Connexin 43 differentially regulates epileptiform activity in models of convulsive and non-convulsive epilepsies. Front Cell Neurosci. 2019;13:173.
Szabó Z, et al. Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo. Sci Rep. 2017;7:6018.
Kutova OM, Pospelov AD, Balalaeva IV. The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance. Biology (Basel). 2023;12:204.
Sirnes S, et al. DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics. 2011;6:602–9.
Tishchenko A, et al. Cx43 and associated cell signaling pathways regulate tunneling nanotubes in breast cancer cells. Cancers (Basel). 2020;12:2798.
Simon Á, Magyar C, Héja L, Kardos J. Peptide Binding Sites of Connexin Proteins. Chemistry (Easton). 2020;2:662–73.
Kékesi O, Ioja EEE, Szabó Z, Kardos J, Héja L. Recurrent seizure-like events are associated with coupled astroglial synchronization. Front Cell Neurosci. 2015;9:215.
Steinhäuser C et al. Astrocyte dysfunction in epilepsy. Jasper’s Basic Mechanisms of the Epilepsies. 2012;63:261–281 http://www.ncbi.nlm.nih.gov/pubmed/22787636.
Hirrlinger J, Nimmerjahn A. A perspective on astrocyte regulation of neural circuit function and animal behavior. Glia. 2022;70:1554–80.
Jourdeuil K, Taneyhill LA. The gap junction protein connexin 43 controls multiple aspects of cranial neural crest cell development. J Cell Sci. 2020;133:jcs235440.
Kunduri G, et al. Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants. Proc Natl Acad Sci U S A. 2018;115:E8919–28.
Walrave L, Vinken M, Leybaert L & Smolders I. Astrocytic connexin43 channels as candidate targets in epilepsy treatment. Biomolecules2020;10. https://doi.org/10.3390/biom10111578.
Lee HJ, et al. Cryo-EM structure of human Cx31.3/GJC3 connexin hemichannel. Sci Adv. 2020;6:eaba4996.
Qi C, et al. Structure of the connexin-43 gap junction channel in a putative closed state. Elife. 2023;12:RP87616.
Lee HJ, et al. Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM. Nat Commun. 2023;14:931.
Héja L, Simon Á, Szabó Z, Kardos J. Connexons coupling to gap junction channel: Potential role for extracellular protein stabilization centers. Biomolecules. 2022;12:49.
Abkevich VI, Shakhnovich EI. What can disulfide bonds tell us about protein energetics, function and folding: Simulations and bioninformatics analysis. J Mol Biol. 2000;300:975–85.
Appenzeller-Herzog C & Riemer J. CHAPTER 1.2. Techniques to Monitor Disulfide Bond Formation and the Reduction Potential of Cysteine–Cystine Couples In vitro and In vivo . in. 2018. https://doi.org/10.1039/9781788013253-00034.
Sun M. an, et al. Prediction of reversible disulfide based on features from local structural signatures. BMC Genomics. 2017;18:279.
Wiedemann C, Kumar A, Lang A & Ohlenschläger O. Cysteines and Disulfide Bonds as Structure-Forming Units: Insights From Different Domains of Life and the Potential for Characterization by NMR. Front Chem.2020;8. https://doi.org/10.3389/fchem.2020.00280.
Østergaard H, Henriksen A, Hansen FG, Winther JR. Shedding light on disulfide bond formation: Engineering a redox switch in green fluorescent protein. EMBO J. 2001;20:5853–62.
Karimi M, et al. Reactivity of disulfide bonds is markedly affected by structure and environment: Implications for protein modification and stability. Sci Rep. 2016;6:38572.
Bao X, Chen Y, Reuss L, Altenberg GA. Functional Expression in Xenopus Oocytes of Gap-junctional Hemichannels Formed by a Cysteine-less Connexin 43. J Biol Chem. 2004;279:9689–92.
Stelzl LS, Fowler PW, Sansom MSP, Beckstein O. Flexible gates generate occluded intermediates in the transport cycle of LacY. J Mol Biol. 2014;426:735–51.
Smart OS, Neduvelil JG, Wang X, Wallace BA, Sansom MSP. HOLE: A program for the analysis of the pore dimensions of ion channel structural models. J Mol Graph. 1996;14:354–60.
Khan AK, et al. A Steric, “Ball-and-Chain” Mechanism for pH-Mediated Regulation of Gap Junction Channels. Cell Rep. 2020;31:107482.
Miyazawa A, Fujiyoshi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003;423:949–55.
Weber PA, Chang HC, Spaeth KE, Nitsche JM, Nicholson BJ. The permeability of gap junction channels to probes of different size is dependent on connexin composition and permeant-pore affinities. Biophys J. 2004;87:958–73.
Keßler M, Wittig I, Ackermann J, Koch I. Prediction and analysis of redox-sensitive cysteines using machine learning and statistical methods. Biol Chem. 2021;402:925–35.
Garrido Ruiz D, Sandoval-Perez A, Rangarajan AV, Gunderson EL, Jacobson MP. Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation. Biochemistry. 2022;61:2165–76.
Wensien M, et al. A lysine–cysteine redox switch with an NOS bridge regulates enzyme function. Nature. 2021;593:460–4.
Rabe von Pappenheim F, et al. Widespread occurrence of covalent lysine–cysteine redox switches in proteins. Nat Chem Biol. 2022;18:368–75.
Mazmanian K, Sargsyan K, Grauffel C, Dudev T, Lim C. Preferred Hydrogen-Bonding Partners of Cysteine: Implications for Regulating Cys Functions. J Phys Chem B. 2016;120:10288–96.
Fra A, Yoboue ED, Sitia R. Cysteines as redox molecular switches and targets of disease. Front. Mol Neurosci. 2017;10. https://doi.org/10.3389/fnmol.2017.00167.
Held JM. Redox Systems Biology: Harnessing the Sentinels of the Cysteine Redoxome. Antioxid Redox Signal. 2020;32. https://doi.org/10.1089/ars.2019.7725.
Groitl B, Jakob U. Thiol-based redox switches. Biochim Biophys Acta Proteins Proteomics. 2014;1844.https://doi.org/10.1016/j.bbapap.2014.03.007.
Careri G, Fasella P, Gratton E, Jencks WP. Statistical time events in enzymes: a physical assessment. CRC Crit Rev Biochem. 1975;3:141–64.
Levin L, et al. A Single Disulfide Bond Disruption in the β3 Integrin Subunit Promotes Thiol/Disulfide Exchange, a Molecular Dynamics Study. PLoS One. 2013;8:e59175.
Nakagawa S, et al. Asparagine 175 of connexin32 is a critical residue for docking and forming functional heterotypic gap junction channels with connexin26. J Biol Chem. 2011;286:19672–81.
Gong XQ, Nakagawa S, Tsukihara T, Bai D. A mechanism of gap junction docking revealed by functional rescue of a human-disease-linked connexin mutant. J Cell Sci. 2013;126:3113–20.
Jassim A, Aoyama H, Ye WG, Chen H, Bai D. Engineered Cx40 variants increased docking and function of heterotypic Cx40/Cx43 gap junction channels. J Mol Cell Cardiol. 2016;90:11–20.
Luscombe NM, Laskowski RA, Thornton JM. Amino acid-base interactions: A three-dimensional analysis of protein-DNA interactions at an atomic level. Nucleic Acids Res. 2001;29:2860.
Flores JA, et al. Connexin-46/50 in a dynamic lipid environment resolved by CryoEM at 1.9 Å. Nat Commun. 2020;11:4331.
Totland MZ, Rasmussen NL, Knudsen LM, Leithe E. Regulation of gap junction intercellular communication by connexin ubiquitination: physiological and pathophysiological implications. Cell Mol Life Sci.2020; 77. https://doi.org/10.1007/s00018-019-03285-0.
Lampe PD, Lau AF. The effects of connexin phosphorylation on gap junctional communication. Int J Biochemi Cell Biol. 2004;36. https://doi.org/10.1016/S1357-2725(03)00264-4.
Liang WG, et al. Human Connexin30.2/31.3 (GJC3) does not Form Functional Gap Junction Channels but Causes Enhanced ATP Release in HeLa Cells. Cell Biochem Biophys. 2011;61:189–97.
Krishnan S, et al. Design of reversible, cysteine-targeted michael acceptors guided by kinetic and computational analysis. J Am Chem Soc. 2014;136:12624–30.
Shindo N, et al. Selective and reversible modification of kinase cysteines with chlorofluoroacetamides. Nat Chem Biol. 2019;15:250–8.
Sõrmus T, et al. Construction of Covalent Bisubstrate Inhibitor of Protein Kinase Reacting with Cysteine Residue at Substrate-Binding Site. J Med Chem. 2022;65:10975–91.
Karaj E, et al. Tunable Cysteine-Targeting Electrophilic Heteroaromatic Warheads Induce Ferroptosis. J Med Chem. 2022;65:11788–817.
Sanderson K. Irreversible kinase inhibitors gain traction. Nat Rev Drug Discov. 2013;12. https://doi.org/10.1038/nrd4103.
Hösli L, et al. Decoupling astrocytes in adult mice impairs synaptic plasticity and spatial learning. Cell Rep. 2022;38:110484.
Zhao Z, Ukidve A, Kim J, Mitragotri S. Targeting Strategies for Tissue-Specific Drug Delivery. Cell. 2020;181. https://doi.org/10.1016/j.cell.2020.02.001.
Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL. OPM database and PPM web server: Resources for positioning of proteins in membranes. Nucleic Acids Res. 2012;40:D370–6.
Bowers KJ. et al. Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. in Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, SC’06 43–43 (Institute of Electrical and Electronics Engineers (IEEE), 2007. https://doi.org/10.1109/sc.2006.54.
Maeda S, et al. Structure of the connexin 26 gap junction channel at 3.5 Å resolution. Nature. 2009;458:597–602.
Humphrey W, Dalke A, Schulten K. VMD: Visual molecular dynamics. J Mol Graph. 1996;14:33–8.
Dosztányi Z, Fiser A, Simon I. Stabilization centers in proteins: Identification, characterization and predictions. J Mol Biol. 1997;272:597–612.
Magyar C, Gromiha MM, Pujadas G, Tusnády GE, Simon I. SRide: A server for identifying stabilizing residues in proteins. Nucleic Acids Res.2005;33:597–612.