期刊
JOURNAL OF PHYSICAL CHEMISTRY B
卷 122, 期 30, 页码 7463-7474出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jpcb.8b03842
关键词
-
资金
- National Science Foundation [ACI-1053575]
- NSF CAREER [CBET-1453312]
- Syracuse University
Tight junction (TJ) protein assembly controls permeability across epithelial and endothelial cells; thus, biochemical interactions that control the TJ assembly have physiological and biomedical significance. In this work, we employed multiscale simulations to probe the TJ self-assembly of five classic claudins (-1, -2, -4, -15, and -19). Claudin proteins assembled into dimeric and occasionally trimeric interfaces that subsequently formed larger polymeric strands. Using orientation-angle analysis to decompose polymeric strands, we found that individual claudins prefer certain dimer interfaces to others. Despite variations in the exact dimer populations observed in individual claudins, there appears to be an overall conformational uniformity in the type of dimeric interactions formed by the claudin family of proteins. A detailed structural characterization of the trimeric assemblies revealed that they could be putative receptors for trimeric Clostridium perfringens enterotoxin. Full characterization of the claudin-2 dimer interface revealed a cysteine cross-linkable interaction, which could be assembled into a symmetric pore of 7.4 angstrom average diameter. We extended the analysis of pore structure to other classic claudins and found that the distribution of polar residues lining the pore volume varied considerably between the barrier- and pore-forming claudins, potentially delineating the functionality in classic claudins.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据