5ER7

Connexin-26 Bound to Calcium

Summary for 5ER7

• Entry DOI: 10.2210/pdb5er7/pdb
• Related: 5ERA
• Descriptor: Gap junction beta-2 protein, CALCIUM ION (2 entities in total)
• Functional Keywords: gap junction, ion channel, calcium binding, electrostatic gating, calcium binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 52357.85

Authors

Purdy, M.D.,Bennett, B.C.,Baker, K.A.,Yeager, M.J. (deposition date: 2015-11-13, release date: 2016-01-27, Last modification date: 2024-11-06)

Primary citation

Bennett, B.C.,Purdy, M.D.,Baker, K.A.,Acharya, C.,McIntire, W.E.,Stevens, R.C.,Zhang, Q.,Harris, A.L.,Abagyan, R.,Yeager, M.
An electrostatic mechanism for Ca(2+)-mediated regulation of gap junction channels.
Nat Commun, 7:8770-8770, 2016

PubMed Abstract: 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 Ca(2+) blocks intercellular communication during tissue injury, we determined the X-ray crystal structures of the human Cx26 gap junction channel with and without bound Ca(2+). The two structures were nearly identical, ruling out both a large-scale structural change and a local steric constriction of the pore. Ca(2+) coordination sites reside at the interfaces between adjacent subunits, near the entrance to the extracellular gap, where local, side chain conformational rearrangements enable Ca(2+)chelation. Computational analysis revealed that Ca(2+)-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.

PubMed: 26753910
DOI: 10.1038/ncomms9770

Experimental method

X-RAY DIFFRACTION (3.286 Å)