Sequence analysis reveals how G protein-coupled receptors transduce the signal to the G protein.
Sequence entropy-variability plots based on alignments of very large numbers of sequences-can indicate the location in proteins of the main active site and modulator sites. In the previous article in this issue, we applied this observation to a series of well-studied proteins and concluded that it was possible to detect most of the residues with a known functional role. Here, we apply the method to rhodopsin-like G protein-coupled receptors. Our conclusion is that G protein binding is the main evolutionary constraint on these receptors, and that other ligands, such as agonists, act as modulators. The activation of the receptors can be described as a simple, two-step process, and the residues involved in signal transduction can be identified.
Oliveira
Laerte
L
Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Paiva
Paulo B
PB
Paiva
Antonio C M
AC
Vriend
Gerrit
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D019277:Entropy; D019143:Evolution, Molecular; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D011956:Receptors, Cell Surface; D012243:Rhodopsin; D019204:GTP-Binding Proteins