Modeling the conformational changes underlying channel opening in CFTR.
Modeling the conformational changes underlying channel opening in CFTR.
复制标题
DOI：
10.1371/journal.pone.0074574
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
McCarty NA
中科院分区：
文献类型：
--
作者：
Rahman KS;Cui G;Harvey SC;McCarty NA
Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), the most common life-shortening genetic disease among Caucasians. Although general features of the structure of CFTR have been predicted from homology models, the conformational changes that result in channel opening and closing have yet to be resolved. We created new closed- and open-state homology models of CFTR, and performed targeted molecular dynamics simulations of the conformational transitions in a channel opening event. The simulations predict a conformational wave that starts at the nucleotide binding domains and ends with the formation of an open conduction pathway. Changes in side-chain interactions are observed in all major domains of the protein, and experimental confirmation was obtained for a novel intra-protein salt bridge that breaks near the end of the transition. The models and simulation add to our understanding of the mechanism of ATP-dependent gating in this disease-relevant ion channel.
登录
查看更多内容
影响因子：
16.8
作者：
Baker, Jennifer M. R.;Hudson, Rhea P.;Forman-Kay, Julie D.
通讯作者：
Forman-Kay, Julie D.
DOI：
10.1085/jgp.200609516
发表时间：
2006-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Aubin CN;Linsdell P
通讯作者：
Linsdell P
DOI：
10.1126/science.1168750
发表时间：
2009-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Aller SG;Yu J;Ward A;Weng Y;Chittaboina S;Zhuo R;Harrell PM;Trinh YT;Zhang Q;Urbatsch IL;Chang G
通讯作者：
Chang G
影响因子：
3
作者：
BROOKS, BR;BRUCCOLERI, RE;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
4.8
作者：
Cotten, JF;Welsh, MJ
通讯作者：
Welsh, MJ