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Sequence homologies between nucleotide binding regions of CFTR and G‐proteins suggest structural and functional similarities
Author(s) -
Manavalan Parthasarathy,
Dearborn Dorr G.,
McPherson John M.,
Smith Alan E.
Publication year - 1995
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)00463-j
Subject(s) - cystic fibrosis transmembrane conductance regulator , atp binding cassette transporter , biology , cyclic nucleotide binding domain , nucleotide , sequence (biology) , gtp' , transmembrane domain , genetics , computational biology , biochemistry , transporter , gene , enzyme
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.