Sequence homologies between nucleotide binding regions of CFTR and G‐proteins suggest structural and functional similarities

Sequence homologies between nucleotide binding regions of CFTR and G‐proteins suggest structural and functional similarities
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CFTR 和 G 蛋白的核苷酸结合区之间的序列同源性表明结构和功能的相似性

DOI:
10.1016/0014-5793(95)00463-j
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发表时间:
1995
期刊:
影响因子:
3.5
通讯作者:
Alan E. Smith
Alan E. Smith
中科院分区:
生物学3区
文献类型:
--
作者:
P. Manavalan;D. Dearborn;J. McPherson;Alan E. Smith

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g蛋白和其他gtp结合蛋白的α-亚基与囊性纤维化跨膜传导调节因子(CFTR)核苷酸结合域(NBDs)内的某些区域序列同源性表明,这些蛋白的结构可能相似。CFTR的nbd序列与其他膜转运蛋白的nbd序列一致,形成了结构模型的基础。该模型预测一个保守序列GGQR,其中许多CF突变发生,形成核苷酸结合口袋的一部分,并作为在GTP结合蛋白中观察到的ON/OFF构象开关。此外,基于CFTR第一和第二nbd之间的细微序列差异以及结构-活性数据,我们认为这两个nbd的核苷酸结合位点环境是不同的。
Sequence homology between the α-subunits of G-proteins and other GTP-binding proteins and certain regions within the nucleotide binding domains (NBDs) of cystic fibrosis transmembrane conductance regulator (CFTR) indicates that these protein structures may be similar. A sequence allignment of the NBDs of CFTR and NBDs from other membrane transporters, forms the basis of a structural model. This model predicts that one of the conserved sequences GGQR, within which a number of CF mutations occur, forms part of the nucleotide binding pocket and serves as an ON/OFF conformational switch as observed in GTP binding proteins. Furthermore, based on subtle sequence differences between the first and second NBDs of CFTR and from structure-activity data, we suggest that the nucleotide binding site environments of the two NBDs are different.
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