Entropy and oligomerization in GPCRs.
Evolutionary trace (ET) and entropy are two related methods for analyzing a multiple sequence alignment to determine functionally important residues in proteins. In this article, these methods have been enhanced with a view to reinvestigate the issue ofGPCR dimerization and oligomerization. In particular, cluster analysis has replaced the subjective visual analysis element of the original ET method. Previous applications of the ET method predicted two dimerization interfaces on the external transmembrane lipid-facing region of GPCRs; these were discussed in terms of dimerization and linear oligomers. Removing the subjective element of the ET method gives rise to the prediction of functionally important residues on the external face of each transmembrane helix for a large number of class A GPCRs. These results are consistent with a growing body of experimental information that, taken over many receptor subtypes, has implicated each transmembrane helix in dimeric interactions. In this application, entropy gave superior results to those obtained from the ET method in that its use gives rise to higher z-scores and fewer instances of z-scores below 3.
Thummer
Rajkumar P
RP
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, CO4 3SQ, UK.
Campbell
Matthew P
MP
Dean
Mark K
MK
Frusher
Marie J
MJ
Scott
Paul D
PD
Reynolds
Christopher A
CA
D000818:Animals; D016000:Cluster Analysis; D019281:Dimerization; D019277:Entropy; D019143:Evolution, Molecular; D046911:Macromolecular Substances / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000502:physiology*
D046911:Macromolecular Substances; D043562:Receptors, G-Protein-Coupled