Extracellular domains play different roles in gap junction formation and docking compatibility

被引:46
作者
Bai, Donglin [1 ]
Wang, Ao Hong [1 ]
机构
[1] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada
基金
加拿大自然科学与工程研究理事会; 加拿大健康研究院;
关键词
docking compatibility; gap junction channel; heterotypic gap junction channels; MARIE-TOOTH-DISEASE; MERZBACHER-LIKE-DISEASE; MULTIPLE CONNEXIN PROTEINS; 3.5 ANGSTROM RESOLUTION; HEARING-LOSS; INTERCELLULAR COMMUNICATION; ATRIAL-FIBRILLATION; MISSENSE MUTATION; MIMETIC PEPTIDES; ATRIOVENTRICULAR-CONDUCTION;
D O I
10.1042/BJ20131162
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
GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (El and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that El and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the El domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both El and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.
引用
收藏
页码:1 / 10
页数:10
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