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Receptors coupling to G proteins: Is there a signal behind the sequence?

Florence Horn¹, Eleonora M. van der Wenden², Laerte Oliveira³, Adriaan P. IJzerman², Gerrit Vriend^1,4*.

1. BIOcomputing, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.
2. Division of Medicinal Chemistry, Leiden-Amsterdam Center for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
3. Escola Paulista Medicina, UNIFESP, CP 20388, 04034 São Paulo, Brazil.
4. CMBI, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
*Correspondence to: Gerrit Vriend, CMBI, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands. Telefax: 31 24 3652977, e-mail: Vriend@CMBI.KUN.NL

Proteins: Structure, Function and Genetics 2000 41:448-459. [Medline]

Upon the binding of their ligands, G protein-coupled receptors couple to the heterotrimeric G proteins to transduce a signal. One receptor family may couple to a single G protein subtype and another family to several ones. Is there a signal in the receptor sequence that can give an indication of the G protein subtype selectivity? We used a sequence analysis method on biogenic amine and adenosine receptors and concluded that a weak signal can be detected in receptor families where specialisation for coupling to a given G protein occurred during a recent divergent evolutionary process.