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

FEBS Letters

Dearborn, Dorr G.²  Smith, Alan E.¹  Manavalan, Parthasarathy¹  McPherson, John M.¹ 

[1] Department of Biotherapeutic Product Development, Genzyme Corporation, One Mountain Road, Framingham, MA 01701, USA;Departments of Pediatrics and Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA

关键词: Cystic fibrosis transmembrane conductane regulator;    Nucleotide binding;    Conformational switch;   

DOI  :  10.1016/0014-5793(95)00463-J

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown