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典型文献
The cation-π interaction in cysteine-rich domain of Smoothened is critical for its cholesterylation and function
文献摘要:
The Hedgehog(Hh)signaling pathway is critical for embryonic development and tissue renewal.The G protein-coupled receptor(GPCR)-like protein Smoothened(SMO)is the central signal transducer in the Hh pathway.Cholesterol binds and then covalently links to the D95 residue of cysteine-rich domain(CRD)of human SMO.The cholesterylation of CRD is critical for SMO activation.SMO cholesterylation is a Ca2+-boosted autoreaction that requires the formation of an ester bond between the side chains of D95 and Y130 as an intermediate.It is unknown whether other residues of SMO are involved in the esterification between D95 and cholesterol.In this study,we find that the SMO-CRD(27-192)can undergo cholesterylation.In addition to D95 and Y130,the residues critical for cholesterol modification include Y85,T88,T90,W109,W119,K133,E160 and F166.T88,W109,W119 and F166 also seem to be involved in protein folding.Notably,we find that Y85 and K133 form a cation-π interaction whose disruption abolishes cholesterylation and ciliary localization of SMO.This study highlights the mechanism and function of cholesterol modification of SMO.
文献关键词:
作者姓名:
Zekai Kong;Min Xu;Yanqing Zhang;Wenda Huang;Xiaolu Zhao;Jie Luo;Bao-Liang Song
作者机构:
Hubei Key Laboratory of Cell Homeostasis,College of Life Sciences,TaiKang Center for Life and Medical Sciences,TaiKang Medical School,Wuhan University,Wuhan 430071,China
引用格式:
[1]Zekai Kong;Min Xu;Yanqing Zhang;Wenda Huang;Xiaolu Zhao;Jie Luo;Bao-Liang Song-.The cation-π interaction in cysteine-rich domain of Smoothened is critical for its cholesterylation and function)[J].生物化学与生物物理学报(英文版),2022(08):1171-1179
A类:
cholesterylation,autoreaction,Y130,Y85,T88,W109,W119,K133,E160,F166
B类:
interaction,cysteine,rich,domain,Smoothened,critical,its,function,Hedgehog,Hh,signaling,pathway,embryonic,development,tissue,renewal,protein,coupled,receptor,GPCR,like,SMO,central,transducer,Cholesterol,binds,covalently,links,D95,CRD,human,activation,Ca2+,boosted,that,requires,formation,bond,between,side,chains,as,intermediate,It,unknown,whether,other,residues,are,involved,esterification,cholesterol,In,this,study,find,can,undergo,addition,modification,include,T90,also,seem,folding,Notably,whose,disruption,abolishes,ciliary,localization,This,highlights,mechanism
AB值:
0.39885
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