Structure of cardiac gap junction intercellular channels

被引:90
作者
Yeager, M
机构
[1] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
[2] Scripps Clin, Div Cardiovasc Dis, La Jolla, CA 92037 USA
基金
美国国家卫生研究院;
关键词
connexins; gap junctions; intercellular communication; crystallization; electron microscopy; cryocrystallography; image analysis;
D O I
10.1006/jsbi.1998.3972
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gap junction proteins, termed connexins, constitute a multigene family of polytopic membrane channel proteins that have four hydrophobic transmembrane domains with the N- and C-termini located on the cytoplasmic membrane face. The principal gap junction protein in the heart, alpha(1) connexin (also designated Cx43), mediates action potential propagation between cells in order to synchronize cardiac contraction. alpha(1) connexin channels are concentrated in gap junction plaques located in the intercalated disks. The intercellular channel is formed by the docking of two hemi-channels, termed connexons, formed by a ring of six 43-kDa alpha(1) connexin subunits. Each subunit is asymmetric with an axial ratio of 4-5:1 with similar to 20 Angstrom extending into the extracellular gap similar to 50 Angstrom spanning the lipid bilayer and similar to 50 Angstrom extending into the cytoplasmic space. We have recently grown two-dimensional crystals of a recombinant C-terminal truncation mutant of alpha(1) connexin (designated alpha(1)Cx263T) that are ordered to better than 7 Angstrom resolution. Projection density maps derived by electron cryocrystallography revealed that the intercellular channel is lined by six alpha-helices, and there is a second ring of six alpha-helices at the interface with the membrane lipids. These rings of alpha-helices are staggered by 30 degrees, which predicts that the two connexons in the channel are staggered by 30 degrees such that each connexin subunit in one connexon interacts with two subunits in the apposed connexon. Such a quaternary arrangement may confer stability in the docking of the connexons to form a tight electrical seal for intercellular current flow during cardiac conduction. (C) 1998 Academic Press.
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页码:231 / 245
页数:15
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