Comparative analysis of the regions binding beta gamma-subunits in Galpha and PH domains.
Some of the pleckstrin homology (PH) domains are shown to bind beta gamma-subunits of a G-protein. In this paper we present a detailed comparison of sequences and structural features of beta gamma-binding regions in PH domains and alpha-subunits (G alpha) of known structure. Our comparison involves switch II region in G alpha and a C-terminal region of PH domain structures and we suggest a similarity in these regions. By comparing the active and inactive forms of G alpha structures we predict that some of the bulky hydrophobic residues in switch II region might interact with beta gamma-subunits. Subsequent to completion of this work we find that this prediction is absolutely consistent with recently reported crystal structures of heterotrimeric G-proteins. We discuss the feasibility of common principles in the recognition G alpha and PH domains by beta gamma-subunits.
Srinivasan
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ICRF Unit of Structural Molecular Biology, Department of Crystallography, Birkbeck College, University of London, United Kingdom.
Waterfield
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Blundell
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry*; D003196:Computer Graphics; D016208:Databases, Factual; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008961:Models, Structural; D008969:Molecular Sequence Data; D010750:Phosphoproteins; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D012984:Software; D015293:Transducin / Q000737:chemistry; D018909:src Homology Domains
D001798:Blood Proteins; D046911:Macromolecular Substances; D010750:Phosphoproteins; C039077:platelet protein P47; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D015293:Transducin; D034281:Dynamins