Molecular determinants in pleckstrin homology domains that allow specific recognition of phosphoinositides.
More than 250 pleckstrin homology (PH) domains have been identified in the human proteome. All PH domains studied to date appear to bind phosphoinositides, most binding only weakly and non-specifically. Members of a small subclass of PH domains show both high affinity and specificity for particular phosphoinositides, and recent structural studies have provided detailed views of these specific interactions. We discuss the architecture of the specific phosphoinositide-binding sites of PH domains, and how selectivity can be modulated by sequence changes.
Lemmon
M A
MA
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6059, USA. mlemmon@mail.med.upenn.edu
Ferguson
K M
KM
D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D020543:Proteome; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D001798:Blood Proteins; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D020543:Proteome; C039077:platelet protein P47; D019869:Phosphatidylinositol 3-Kinases