Lipid-facing correlated mutations and dimerization in G-protein coupled receptors.
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.
Gouldson
P R
PR
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK.
Dean
M K
MK
Snell
C R
CR
Bywater
R P
RP
Gkoutos
G
G
Reynolds
C A
CA
D000595:Amino Acid Sequence; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D008055:Lipids; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D020836:Protein Structure, Quaternary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011957:Receptors, Opioid / Q000737:chemistry / Q000235:genetics; D017481:Receptors, Somatostatin / Q000737:chemistry / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D008055:Lipids; D011956:Receptors, Cell Surface; D011957:Receptors, Opioid; D017481:Receptors, Somatostatin; D011989:Receptors, Thyrotropin; D019204:GTP-Binding Proteins