[PH domain: a new functional domain].
A pleckstrin homology (PH) domain is an approximately 100 amino acid region of sequence homology present in numerous proteins involved in signal transduction and growth control. The three dimensional structures of several PH domains demonstrate that they consist of a beta-barrel of seven antiparallel beta-sheets and a carboxyl-terminal amphiphilic alpha-helix. Several ligands capable of binding to PH domains have been identified including phosphatidylinositol 4,5-bisphosphate and the beta gamma subunits of heterotrimeric G proteins, which bind to the amino and carboxyl-termini of the PH domain, respectively. Furthermore, several isoforms of protein kinase C appear to bind to some PH domains. A general function of PH domains may be to anchor PH domain-containing proteins to the appropriate membrane-compartment. The membrane localization of PH domain-containing proteins may require cooperative multiple ligand binding to the PH domain. Finally, the heterogeneity of sequences among various PH domains may prove to be the basis for differences in the regulation and specificity of PH domain-ligand interaction in a fashion similar to SH2 and SH3 domains. The function of the PH domain and the mechanisms of PH domain action seem to be quite complex.
Touhara
K
K
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
D000818:Animals; D001665:Binding Sites; D008024:Ligands; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D008024:Ligands; D011506:Proteins; D011493:Protein Kinase C