An electrostatic mechanism for Ca2+-mediated regulation of gap junction channels

Bennett, Brad C.; Purdy, Michael D.; Baker, Kent A.; Acharya, Chayan; McIntire, William E.; Stevens, Raymond C.; Zhang, Qinghai; Harris, Andrew L.; Abagyan, Ruben; Yeager, Mark

doi:10.1038/ncomms9770

Title: An electrostatic mechanism for Ca²⁺-mediated regulation of gap junction channels

Journal Article · Tue Jan 12 00:00:00 EST 2016 · Nature Communications

DOI:https://doi.org/10.1038/ncomms9770· OSTI ID:1235480

Bennett, Brad C. ^[1]; Purdy, Michael D. ^[2]; Baker, Kent A. ^[3]; Acharya, Chayan ^[4]; McIntire, William E. ^[2]; Stevens, Raymond C. ^[5]; Zhang, Qinghai ^[3]; Harris, Andrew L. ^[6]; Abagyan, Ruben ^[4]; Yeager, Mark ^[7]

Samford Univ., Birmingham, AL (United States); Univ. of Virginia School of Medicine, Charlottesville, VA (United States)
Univ. of Virginia School of Medicine, Charlottesville, VA (United States)
The Scripps Research Inst., La Jolla, CA (United States)
Univ. of California at San Diego, La Jolla, CA (United States)
Univ. of Southern California, Los Angeles, CA (United States)
Rutgers New Jersey Medical School, Newark, NJ (United States)
Univ. of Virginia School of Medicine, Charlottesville, VA (United States); The Scripps Research Inst., La Jolla, CA (United States)

Gap junction channels mediate intercellular signalling that is crucial in tissue development, homeostasis and pathologic states such as cardiac arrhythmias, cancer and trauma. To explore the mechanism by which Ca²⁺ blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca²⁺. The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca²⁺ coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca²⁺chelation. Computational analysis revealed that Ca²⁺-binding generates a positive electrostatic barrier that substantially inhibits permeation of cations such as K⁺ into the pore. Our results provide structural evidence for a unique mechanism of channel regulation: ionic conduction block via an electrostatic barrier rather than steric occlusion of the channel pore.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Cancer Inst.; National Inst. of General Medical Sciences

Grant/Contract Number:: W-31-109-Eng-38; R01 HL048908; R01 GM098538; R01 GM071872; P50 GM073197; Y1-CO-1020; Y1-GM-1104

OSTI ID:: 1235480

Journal Information:: Nature Communications, Vol. 7, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

Citation Metrics:

Cited by: 95 works

Citation information provided by
Web of Science

References (65)

CHARMM: the biomolecular simulation program Brooks, B. R.; Brooks, C. L.; Mackerell, A. D. Wiley-Blackwell https://doi.org/10.5167/uzh-19245	text	January 2009
Linking Crystallographic Model and Data Quality Karplus, P. A.; Diederichs, K. Science, Vol. 336, Issue 6084 https://doi.org/10.1126/science.1218231	journal	May 2012
Gap junction regulation by calmodulin Zou, Juan; Salarian, Mani; Chen, Yanyi FEBS Letters, Vol. 588, Issue 8 https://doi.org/10.1016/j.febslet.2014.01.003	journal	January 2014
Gap Junction Channels and Cardiac Impulse Propagation Desplantez, Thomas; Dupont, Emmanuel; Severs, Nicholas J. Journal of Membrane Biology, Vol. 218, Issue 1-3 https://doi.org/10.1007/s00232-007-9046-8	journal	July 2007
A fast adaptive multigrid boundary element method for macromolecular electrostatic computations in a solvent Vorobjev, Yury N.; Scheraga, Harold A. Journal of Computational Chemistry, Vol. 18, Issue 4 https://doi.org/10.1002/(sici)1096-987x(199703)18:4<569::aid-jcc10>3.0.co;2-b	journal	March 1997
Gap junction permeability: selectivity for anionic and cationic probes Kanaporis, G.; Brink, P. R.; Valiunas, V. American Journal of Physiology-Cell Physiology, Vol. 300, Issue 3 https://doi.org/10.1152/ajpcell.00316.2010	journal	March 2011
Late sodium current in the pathophysiology of cardiovascular disease: consequences of sodium-calcium overload Noble, D. Heart, Vol. 92, Issue suppl_4 https://doi.org/10.1136/hrt.2005.078782	journal	July 2006
Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions. Saez, J. C.; Connor, J. A.; Spray, D. C. Proceedings of the National Academy of Sciences, Vol. 86, Issue 8 https://doi.org/10.1073/pnas.86.8.2708	journal	April 1989
Conformational changes in surface structures of isolated connexin 26 gap junctions Muller, D. J. The EMBO Journal, Vol. 21, Issue 14 https://doi.org/10.1093/emboj/cdf365	journal	July 2002
Molecular determinants of membrane potential dependence in vertebrate gap junction channels Revilla, A.; Bennett, M. V. L.; Barrio, L. C. Proceedings of the National Academy of Sciences, Vol. 97, Issue 26 https://doi.org/10.1073/pnas.97.26.14760	journal	December 2000
The role of connexins in ear and skin physiology — Functional insights from disease-associated mutations Xu, Ji; Nicholson, Bruce J. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1828, Issue 1 https://doi.org/10.1016/j.bbamem.2012.06.024	journal	January 2013
Gap junctional conductance: comparison of sensitivities to H and Ca ions. Spray, D. C.; Stern, J. H.; Harris, A. L. Proceedings of the National Academy of Sciences, Vol. 79, Issue 2 https://doi.org/10.1073/pnas.79.2.441	journal	January 1982
Asparagine 175 of Connexin32 Is a Critical Residue for Docking and Forming Functional Heterotypic Gap Junction Channels with Connexin26 Nakagawa, So; Gong, Xiang-Qun; Maeda, Shoji Journal of Biological Chemistry, Vol. 286, Issue 22 https://doi.org/10.1074/jbc.m110.204958	journal	April 2011
Loop Gating of Connexin Hemichannels Involves Movement of Pore-lining Residues in the First Extracellular Loop Domain Verselis, Vytas K.; Trelles, Maria P.; Rubinos, Clio Journal of Biological Chemistry, Vol. 284, Issue 7 https://doi.org/10.1074/jbc.m807430200	journal	December 2008
Gap Junctions Mediate Glucose Transport Between GLUT1-Positive and -Negative Cells in the Spiral Limbus of the Rat Cochlea Matsunami, Tatsuya; Suzuki, Toshihiro; Hisa, Yasuo Cell Communication & Adhesion, Vol. 13, Issue 1-2 https://doi.org/10.1080/15419060600631805	journal	January 2006
CHARMM: The biomolecular simulation program Brooks, B. R.; Brooks, C. L.; Mackerell, A. D. Journal of Computational Chemistry, Vol. 30, Issue 10 https://doi.org/10.1002/jcc.21287	journal	July 2009
Coupling asymmetry of heterotypic connexin 45/ connexin 43-EGFP gap junctions: Properties of fast and slow gating mechanisms Bukauskas, F. F.; Bukauskiene, A.; Verselis, V. K. Proceedings of the National Academy of Sciences, Vol. 99, Issue 10 https://doi.org/10.1073/pnas.032062099	journal	May 2002
Two configurations of a channel-forming membrane protein Unwin, P. N. T.; Ennis, P. D. Nature, Vol. 307, Issue 5952 https://doi.org/10.1038/307609a0	journal	February 1984
Three-Dimensional Structure of a Recombinant Gap Junction Membrane Channel Unger, V. M. Science, Vol. 283, Issue 5405 https://doi.org/10.1126/science.283.5405.1176	journal	February 1999
Conformational changes in a pore-forming region underlie voltage-dependent “loop gating” of an unapposed connexin hemichannel Tang, Qingxiu; Dowd, Terry L.; Verselis, Vytas K. The Journal of General Physiology, Vol. 133, Issue 6 https://doi.org/10.1085/jgp.200910207	journal	May 2009
The CCP4 suite programs for protein crystallography Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
Connexin channels and phospholipids: association and modulation Locke, Darren; Harris, Andrew L. BMC Biology, Vol. 7, Issue 1 https://doi.org/10.1186/1741-7007-7-52	journal	August 2009
National variations in cardiac service provision: how united is our kingdom? Norell, M. S. Heart, Vol. 92, Issue 1 https://doi.org/10.1136/hrt.2005.070292	journal	January 2006
Characterization of the pH-dependent Interaction between the Gap Junction Protein Connexin43 Carboxyl Terminus and Cytoplasmic Loop Domains Hirst-Jensen, Bethany J.; Sahoo, Prangya; Kieken, Fabien Journal of Biological Chemistry, Vol. 282, Issue 8 https://doi.org/10.1074/jbc.m605233200	journal	December 2006
Biological and Biophysical Properties of Vascular Connexin Channels Johnstone, Scott; Isakson, Brant; Locke, Darren International Review of Cell and Molecular Biology https://doi.org/10.1016/S1937-6448(09)78002-5	book	January 2009
A Cα Model for the Transmembrane α Helices of Gap Junction Intercellular Channels Fleishman, Sarel J.; Unger, Vinzenz M.; Yeager, Mark Molecular Cell, Vol. 15, Issue 6 https://doi.org/10.1016/j.molcel.2004.08.016	journal	September 2004
Molecular Dynamics and Brownian Dynamics Investigation of Ion Permeation and Anesthetic Halothane Effects on a Proton-Gated Ion Channel Cheng, Mary Hongying; Coalson, Rob D.; Tang, Pei Journal of the American Chemical Society, Vol. 132, Issue 46 https://doi.org/10.1021/ja105001a	journal	November 2010
Mechanism for modulation of gating of connexin26-containing channels by taurine Locke, Darren; Kieken, Fabien; Tao, Liang The Journal of General Physiology, Vol. 138, Issue 3 https://doi.org/10.1085/jgp.201110634	journal	August 2011
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
Cochlear gap junctions coassembled from Cx26 and 30 show faster intercellular Ca ²⁺ signaling than homomeric counterparts Sun, Jianjun; Ahmad, Shoab; Chen, Shanping American Journal of Physiology-Cell Physiology, Vol. 288, Issue 3 https://doi.org/10.1152/ajpcell.00341.2004	journal	March 2005
The First Extracellular Loop Domain Is a Major Determinant of Charge Selectivity in Connexin46 Channels Trexler, E. Brady; Bukauskas, Feliksas F.; Kronengold, Jack Biophysical Journal, Vol. 79, Issue 6, p. 3036-3051 https://doi.org/10.1016/S0006-3495(00)76539-8	journal	December 2000
Steroid-based facial amphiphiles for stabilization and crystallization of membrane proteins Lee, S. C.; Bennett, B. C.; Hong, W. -X. Proceedings of the National Academy of Sciences, Vol. 110, Issue 13 https://doi.org/10.1073/pnas.1221442110	journal	March 2013
Gap junctional conductance is a simple and sensitive function of intracellular pH Spray, D.; Harris, A.; Bennett, M. Science, Vol. 211, Issue 4483 https://doi.org/10.1126/science.6779379	journal	February 1981
Calcium-mediated changes in gap junction structure: evidence from the low angle X-ray pattern. Unwin, P. N.; Ennis, P. D. The Journal of Cell Biology, Vol. 97, Issue 5 https://doi.org/10.1083/jcb.97.5.1459	journal	November 1983
Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness Kikuchi, T.; Adams, Joe C.; Miyabe, Yuka Medical Electron Microscopy, Vol. 33, Issue 2 https://doi.org/10.1007/s007950070001	journal	November 2000
Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36 Palacios-Prado, Nicolás; Chapuis, Sandrine; Panjkovich, Alejandro Nature Communications, Vol. 5, Issue 1 https://doi.org/10.1038/ncomms5667	journal	August 2014
Decoupling of heart muscle cells: Correlation with increased cytoplasmic calcium activity and with changes of nexus ultrastructure Dahl, Gerhard; Isenberg, Gerrit The Journal of Membrane Biology, Vol. 53, Issue 1 https://doi.org/10.1007/bf01871173	journal	February 1980
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Gap junction-mediated intercellular diffusion of Ca2+ in cultured human corporal smooth muscle cells Christ, G. J.; Moreno, A. P.; Melman, A. American Journal of Physiology-Cell Physiology, Vol. 263, Issue 2 https://doi.org/10.1152/ajpcell.1992.263.2.c373	journal	August 1992
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
Statistical analysis of structural characteristics of protein Ca2+-binding sites Kirberger, Michael; Wang, Xue; Deng, Hai JBIC Journal of Biological Inorganic Chemistry, Vol. 13, Issue 7 https://doi.org/10.1007/s00775-008-0402-7	journal	July 2008
The gap junction channel. Its aqueous nature as indicated by deuterium oxide effects Verselis, V.; Brink, P. R. Biophysical Journal, Vol. 50, Issue 5 https://doi.org/10.1016/s0006-3495(86)83542-1	journal	November 1986
Rapid boundary element solvation electrostatics calculations in folding simulations: Successful folding of a 23-residue peptide Totrov, Maxim; Abagyan, Ruben Biopolymers, Vol. 60, Issue 2 https://doi.org/10.1002/1097-0282(2001)60:2<124::AID-BIP1008>3.0.CO;2-S	journal	January 2001
Kinetic properties of a voltage-dependent junctional conductance. Harris, A. L.; Spray, D. C.; Bennett, M. V. The Journal of General Physiology, Vol. 77, Issue 1 https://doi.org/10.1085/jgp.77.1.95	journal	January 1981
VDAC channels mediate and gate the flow of ATP: implications for the regulation of mitochondrial function Rostovtseva, T.; Colombini, M. Biophysical Journal, Vol. 72, Issue 5 https://doi.org/10.1016/S0006-3495(97)78841-6	journal	May 1997
Gap junction channels and cardiac impulse propagation Desplantez, Thomas; Dupont, Emmanuel; Severs, Nicholas J. Springer-Verlag https://doi.org/10.7892/boris.22601	text	January 2007
Connexin channel permeability to cytoplasmic molecules Harris, A. Progress in Biophysics and Molecular Biology, Vol. 94, Issue 1-2 https://doi.org/10.1016/j.pbiomolbio.2007.03.011	journal	May 2007
Analytical molecular surface calculation Connolly, M. L. Journal of Applied Crystallography, Vol. 16, Issue 5 https://doi.org/10.1107/S0021889883010985	journal	October 1983
Localization of a Voltage Gate in Connexin46 Gap Junction Hemichannels Pfahnl, Arnold; Dahl, Gerhard Biophysical Journal, Vol. 75, Issue 5 https://doi.org/10.1016/s0006-3495(98)77676-3	journal	November 1998
Small revisions to predicted distances around metal sites in proteins Harding, Marjorie M. Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 6 https://doi.org/10.1107/S0907444906014594	journal	May 2006
Structure of the junction between communicating cells Unwin, P. N. T.; Zampighi, G. Nature, Vol. 283, Issue 5747 https://doi.org/10.1038/283545a0	journal	February 1980
Energy parameters in polypeptides. 10. Improved geometrical parameters and nonbonded interactions for use in the ECEPP/3 algorithm, with application to proline-containing peptides Nemethy, George; Gibson, Kenneth D.; Palmer, Kathleen A. The Journal of Physical Chemistry, Vol. 96, Issue 15 https://doi.org/10.1021/j100194a068	journal	July 1992
Gap Junctions Nielsen, Morten Schak; Axelsen, Lene Nygaard; Sorgen, Paul L. Comprehensive Physiology https://doi.org/10.1002/cphy.c110051	book	July 2012
Structure of the connexin 26 gap junction channel at 3.5 Å resolution Maeda, Shoji; Nakagawa, So; Suga, Michihiro Nature, Vol. 458, Issue 7238 https://doi.org/10.1038/nature07869	journal	April 2009
Gap Junction Channel Structure Yeager, Mark Connexins https://doi.org/10.1007/978-1-59745-489-6_2	book	January 2009
Pharmacology of Connexin Channels Srinivas, Miduturu Connexins https://doi.org/10.1007/978-1-59745-489-6_8	book	January 2009
ICM?A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation Abagyan, Ruben; Totrov, Maxim; Kuznetsov, Dmitry Journal of Computational Chemistry, Vol. 15, Issue 5 https://doi.org/10.1002/jcc.540150503	journal	May 1994
Acetylcholine-like effects of intracellular calcium application in pancreatic acinar cells Iwatsuki, N.; Petersen, O. H. Nature, Vol. 268, Issue 5616 https://doi.org/10.1038/268147a0	journal	July 1977
Different Ionic Selectivities for Connexins 26 and 32 Produce Rectifying Gap Junction Channels Suchyna, Thomas M.; Nitsche, Johannes M.; Chilton, Mark Biophysical Journal, Vol. 77, Issue 6 https://doi.org/10.1016/s0006-3495(99)77129-8	journal	December 1999
Extracellular domains play different roles in gap junction formation and docking compatibility Bai, Donglin; Wang, Ao Hong Biochemical Journal, Vol. 458, Issue 1 https://doi.org/10.1042/bj20131162	journal	January 2014
Two strategies for sequence comparison: profile-preprocessed and secondary structure-induced multiple alignment Heringa, Jaap Computers & Chemistry, Vol. 23, Issue 3-4 https://doi.org/10.1016/s0097-8485(99)00012-1	journal	June 1999
Gap junction channel structure in the early 21st century: facts and fantasies Yeager, Mark; Harris, Andrew L. Current Opinion in Cell Biology, Vol. 19, Issue 5 https://doi.org/10.1016/j.ceb.2007.09.001	journal	October 2007
A Grand Canonical Monte Carlo–Brownian Dynamics Algorithm for Simulating Ion Channels Im, Wonpil; Seefeld, Stefan; Roux, Benoît Biophysical Journal, Vol. 79, Issue 2 https://doi.org/10.1016/S0006-3495(00)76336-3	journal	August 2000
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Gating on the outside Harris, Andrew L. Journal of General Physiology, Vol. 133, Issue 6 https://doi.org/10.1085/jgp.200910256	journal	May 2009

Cited By (40)

Calmodulin-Mediated Regulation of Gap Junction Channels Peracchia, Camillo International Journal of Molecular Sciences, Vol. 21, Issue 2 https://doi.org/10.3390/ijms21020485	journal	January 2020
Connexin Hemichannels in Astrocytes: Role in CNS Disorders Xing, LingYan; Yang, Tuo; Cui, ShuSen Frontiers in Molecular Neuroscience, Vol. 12 https://doi.org/10.3389/fnmol.2019.00023	journal	February 2019
Microarray-based screening system identifies temperature-controlled activity of Connexin 26 that is distorted by mutations Wang, Hongling; Stahl, Frank; Scheper, Thomas Berlin : Springer Nature https://doi.org/10.15488/9326	text	January 2019
Inner Ear Connexin Channels: Roles in Development and Maintenance of Cochlear Function Mammano, Fabio Cold Spring Harbor Perspectives in Medicine, Vol. 9, Issue 7 https://doi.org/10.1101/cshperspect.a033233	journal	September 2018
GAP junctional communication in brain secondary organizers Bosone, Camilla; Andreu, Abraham; Echevarria, Diego Development, Growth & Differentiation, Vol. 58, Issue 5 https://doi.org/10.1111/dgd.12297	journal	June 2016
The syndromic deafness mutation G12R impairs fast and slow gating in Cx26 hemichannels García, Isaac E.; Villanelo, Felipe; Contreras, Gustavo F. Journal of General Physiology, Vol. 150, Issue 5 https://doi.org/10.1085/jgp.201711782	journal	April 2018
On Biophysical Properties and Sensitivity to Gap Junction Blockers of Connexin 39 Hemichannels Expressed in HeLa Cells Vargas, Anibal A.; Cisterna, Bruno A.; Saavedra-Leiva, Fujiko Frontiers in Physiology, Vol. 8 https://doi.org/10.3389/fphys.2017.00038	journal	February 2017
Connexins in Astrocyte Migration Lagos-Cabré, Raúl; Burgos-Bravo, Francesca; Avalos, Ana María Frontiers in Pharmacology, Vol. 10 https://doi.org/10.3389/fphar.2019.01546	journal	January 2020
Modulation of Asymmetric Flux in Heterotypic Gap Junctions by Pore Shape, Particle Size and Charge Mondal, Abhijit; Sachse, Frank B.; Moreno, Alonso P. Frontiers in Physiology, Vol. 8 https://doi.org/10.3389/fphys.2017.00206	journal	April 2017
Innexins: Expression, Regulation, and Functions Güiza, Juan; Barría, Iván; Sáez, Juan C. Frontiers in Physiology, Vol. 9 https://doi.org/10.3389/fphys.2018.01414	journal	October 2018
Structure of a volume-regulated anion channel of the LRRC8 family Deneka, Dawid; Sawicka, Marta; Lam, Andy K. M. Nature Publishing Group https://doi.org/10.5167/uzh-153179	text	January 2018
Gap junction structure: unraveled, but not fully revealed Beyer, Eric C.; Berthoud, Viviana M. F1000Research, Vol. 6 https://doi.org/10.12688/f1000research.10490.1	journal	April 2017
Magnesium interactions with a CX26 connexon in lipid bilayers Albano, Juan M. R.; Facelli, Julio C.; Ferraro, Marta B. Journal of Molecular Modeling, Vol. 25, Issue 8 https://doi.org/10.1007/s00894-019-4121-5	journal	July 2019
Cryo-EM structures of the human volume-regulated anion channel LRRC8 Kasuya, Go; Nakane, Takanori; Yokoyama, Takeshi Nature Structural & Molecular Biology, Vol. 25, Issue 9 https://doi.org/10.1038/s41594-018-0109-6	journal	August 2018
Specific functional pathologies of Cx43 mutations associated with oculodentodigital dysplasia Kelly, John J.; Esseltine, Jessica L.; Shao, Qing Molecular Biology of the Cell, Vol. 27, Issue 14 https://doi.org/10.1091/mbc.e16-01-0062	journal	July 2016
Flow-induced mechanotransduction in skeletal cells Alfieri, Roberta; Vassalli, Massimo; Viti, Federica Biophysical Reviews, Vol. 11, Issue 5 https://doi.org/10.1007/s12551-019-00596-1	journal	September 2019
Modelling of Ca ²⁺ -promoted structural effects in wild type and post-translationally modified Connexin26 Calligari, Paolo; Torsello, Mauro; Bortoli, Marco Molecular Simulation, Vol. 46, Issue 3 https://doi.org/10.1080/08927022.2019.1690653	journal	November 2019
Calmodulin-Mediated Regulation of Gap Junction Channels Peracchia, Camillo Prime Archives in Molecular Biology https://doi.org/10.37247/pamb.1.2020.37	book	January 2020
Atomic structure of the innexin-6 gap junction channel determined by cryo-EM Oshima, Atsunori; Tani, Kazutoshi; Fujiyoshi, Yoshinori Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms13681	journal	December 2016
Microarray-based screening system identifies temperature-controlled activity of Connexin 26 that is distorted by mutations Wang, Hongling; Stahl, Frank; Scheper, Thomas Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-49423-3	journal	September 2019
Loss of Coupling Distinguishes GJB1 Mutations Associated with CNS Manifestations of CMT1X from Those Without CNS Manifestations Abrams, Charles K.; Goman, Mikhail; Wong, Sarah Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/srep40166	journal	January 2017
A structural and functional comparison of gap junction channels composed of connexins and innexins: Structural and Functional Comparison of Gap Junction Channels Skerrett, I. Martha; Williams, Jamal B. Developmental Neurobiology, Vol. 77, Issue 5 https://doi.org/10.1002/dneu.22447	journal	November 2016
Critical role of ATP-induced ATP release for Ca ²⁺ signaling in nonsensory cell networks of the developing cochlea Ceriani, Federico; Pozzan, Tullio; Mammano, Fabio Proceedings of the National Academy of Sciences, Vol. 113, Issue 46 https://doi.org/10.1073/pnas.1616061113	journal	November 2016
The connexin26 human mutation N14K disrupts cytosolic intersubunit interactions and promotes channel opening Valdez Capuccino, Juan M.; Chatterjee, Payal; García, Isaac E. The Journal of General Physiology, Vol. 151, Issue 3 https://doi.org/10.1085/jgp.201812219	journal	December 2018
Structural determinants underlying permeant discrimination of the Cx43 hemichannel Nielsen, Brian Skriver; Zonta, Francesco; Farkas, Thomas Journal of Biological Chemistry, Vol. 294, Issue 45 https://doi.org/10.1074/jbc.ra119.007732	journal	September 2019
Gap Junction Channels of Innexins and Connexins: Relations and Computational Perspectives Sánchez, Alejandro; Castro, Carlos; Flores, Dora-Luz International Journal of Molecular Sciences, Vol. 20, Issue 10 https://doi.org/10.3390/ijms20102476	journal	May 2019
Structure of native lens connexin 46/50 intercellular channels by cryo-EM Myers, Janette B.; Haddad, Bassam G.; O’Neill, Susan E. Nature, Vol. 564, Issue 7736 https://doi.org/10.1038/s41586-018-0786-7	journal	December 2018
Structure of a volume-regulated anion channel of the LRRC8 family Deneka, Dawid; Sawicka, Marta; Lam, Andy K. M. Nature, Vol. 558, Issue 7709 https://doi.org/10.1038/s41586-018-0134-y	journal	May 2018
Accessing gap-junction channel structure-function relationships through molecular modeling and simulations Villanelo, F.; Escalona, Y.; Pareja-Barrueto, C. BMC Cell Biology, Vol. 18, Issue S1 https://doi.org/10.1186/s12860-016-0121-9	journal	January 2017
Therapeutic strategies targeting connexins Laird, Dale W.; Lampe, Paul D. Nature Reviews Drug Discovery, Vol. 17, Issue 12 https://doi.org/10.1038/nrd.2018.138	journal	October 2018
Bioinspired smart asymmetric nanochannel membranes Zhang, Zhen; Wen, Liping; Jiang, Lei Chemical Society Reviews, Vol. 47, Issue 2 https://doi.org/10.1039/c7cs00688h	journal	January 2018
Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas Frontiers in Physiology, Vol. 9 https://doi.org/10.3389/fphys.2018.00362	journal	April 2018
Variable effects of local management on coral defenses against a thermally regulated bleaching pathogen Beatty, Deanna S.; Valayil, Jinu Mathew; Clements, Cody S. Science Advances, Vol. 5, Issue 10 https://doi.org/10.1126/sciadv.aay1048	journal	October 2019
Variants with increased negative electrostatic potential in the Cx50 gap junction pore increased unitary channel conductance and magnesium modulation Tejada, Mary Grace; Sudhakar, Swathy; Kim, Nicholas K. Biochemical Journal, Vol. 475, Issue 21 https://doi.org/10.1042/bcj20180523	journal	November 2018
Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO ₂ de Wolf, Elizabeth; Cook, Jonathan; Dale, Nicholas Proceedings of the Royal Society B: Biological Sciences, Vol. 284, Issue 1848 https://doi.org/10.1098/rspb.2016.2723	journal	February 2017
Cryo-EM structure of the volume-regulated anion channel LRRC8 Kasuya, Go; Nakane, Takanori; Yokoyama, Takeshi bioRxiv https://doi.org/10.1101/331207	posted_content	May 2018
Carbon replicas reveal double stranded structure of tight junctions in phase-contrast electron microscopy Krystofiak, Evan S.; Heymann, J. Bernard; Kachar, Bechara Communications Biology, Vol. 2, Issue 1 https://doi.org/10.1038/s42003-019-0319-4	journal	March 2019
Electrical coupling and its channels Harris, Andrew L. Journal of General Physiology, Vol. 150, Issue 12 https://doi.org/10.1085/jgp.201812203	journal	November 2018
Structure of an innexin gap junction channel and cryo-EM sample preparation Oshima, Atsunori Microscopy, Vol. 66, Issue 6 https://doi.org/10.1093/jmicro/dfx035	journal	September 2017
Comparative functional characterization of novel non-syndromicGJB2gene variant p.Gly45Arg and lethal syndromic variant p.Gly45Glu Rodriguez-Paris, Juan; Waldhaus, Jörg; Gordhandas, Jeenal A. PeerJ, Vol. 4 https://doi.org/10.7717/peerj.2494	journal	October 2016

Similar Records

The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor

Journal Article · Tue Dec 01 00:00:00 EST 2015 · Structure · OSTI ID:1235480

Miller, Rebecca L.; Thompson, Aaron A.; Trapella, Claudio; +8 more

Role of gamma carboxylated Glu47 in connexin 26 hemichannel regulation by extracellular Ca{sup 2+}: Insight from a local quantum chemistry study

Journal Article · Fri Feb 28 00:00:00 EST 2014 · Biochemical and Biophysical Research Communications · OSTI ID:1235480

Zonta, Francesco; Mammano, Fabio; Torsello, Mauro; +3 more

Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic Acid Derivatives Is Dependent on Peroxide Tone

Journal Article · Fri May 20 00:00:00 EDT 2016 · Journal of Biological Chemistry · OSTI ID:1235480

Orlando, Benjamin J.; Malkowski, Michael G.

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Cell signalling
Membrane proteins
Molecular conformation
Structural biology

Title: An electrostatic mechanism for Ca2+-mediated regulation of gap junction channels

Citation Formats

References (65)

Cited By (40)

Similar Records

Related Subjects

Title: An electrostatic mechanism for Ca²⁺-mediated regulation of gap junction channels