Lipid-facing correlated mutations and dimerization in G-protein coupled receptors

被引:47
作者
Gouldson, PR
Dean, MK
Snell, CR
Bywater, RP
Gkoutos, G
Reynolds, CA
机构
[1] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England
[2] Novartis Inst Med Sci, London WC1E 6BN, England
[3] Novo Nordisk AS, Biostruct Dept, DK-2760 Malov, Denmark
来源
PROTEIN ENGINEERING | 2001年 / 14卷 / 10期
关键词
dimerization; G-protein; lipid-facing; mutations; rhodopsin crystal structure;
D O I
10.1093/protein/14.10.759
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A correlated mutation analysis has been performed on the aligned protein sequences of a number of class A G-protein coupled receptor families, including the chemokine, neurokinin, opioid, somatostatin, thyrotrophin and the whole biogenic amine family. Many of the correlated mutations are observed flanking or neighbouring conserved residues. The correlated residues have been plotted onto the transmembrane portion of the rhodopsin crystal structure. The structure shows that a significant proportion of the correlated mutations are located on the external (lipid-facing) region of the helices. The occurrence of these highly correlated patterns of change amongst the external residues suggest that they are sites for protein-protein interactions. In particular, it is suggested that the correlated residues may be involved in either large conformational changes, the formation of heterodimers or homodimers (which may be domain swapped) or oligomers required for activation or internalization. The results are discussed in the light of the subtype-specific heterodimerization observed for the chemokine, opioid and somatostatin receptors.
引用
收藏
页码:759 / 767
页数:9
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