The interaction of class B G protein-coupled receptors with their hormones.
In common with many G protein-coupled receptors, dysfunction in members of the Class B or glucagon-like receptors can elicit a wide spectrum of disease related activities. Consequently, they are potential targets in many different areas of pharmacological research. Unlike the class A or rhodopsin-like receptors, for which at least some structural similarity to bacteriorhodopsin has been detected, absolutely no structural information is available for the Class B G protein-coupled receptors. We present a computational study that exploits the experimental work performed by evolution to indicate residues that are potentially involved in ligand binding in the Class B G protein-coupled receptors. We perform an analysis of mutations that occurred in a correlated fashion between the receptors and their peptidic ligands. The inference that the residues detected in this manner are involved in a direct interaction between the receptor and the ligand is in good agreement with the mutation studies that have already been published.
BIOcomputing, European Molecular Biology Laboratory, Heidelberg, Germany.
F
F
Horn
R
R
Bywater
G
G
Krause
W
W
Kuipers
L
L
Oliveira
A C
AC
Paiva
C
C
Sander
G
G
Vriend
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D019204:GTP-Binding Proteins / Q000502:physiology*; D006728:Hormones / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000502:physiology*; D016415:Sequence Alignment; D017421:Sequence Analysis; D015398:Signal Transduction / Q000502:physiology*
D006728:Hormones; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins