STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN FROM BETA-SPECTRIN

The 'pleckstrin homology' or PH domain is a 100-residue protein module . It is present in many kinases, different isoforms of phospholipase C , GTPase-activating proteins and nucleotide-exchange factors(1-4). Its function is not known, but many proteins that contain a PH domain int eract with GTP-binding proteins(5). The PH domain in beta-adrenergic r eceptor kinase may be involved in binding to the beta gamma subunits o f a trimeric G-protein(3,4,6,7). We report here the three-dimensional structure of the PH domain of the cytoskeletal protein spectrin using homonuclear nuclear magnetic resonance. The core of the molecule is an antiparallel beta-sheet consisting of seven strands. The C terminus i s folded into a long alpha-helix, and another helix is present in one of the surface loops. The molecule is electrostatically polarized and contains a pocket which may be involved in the binding of a ligand. Th ere is a distant relationship to the peptidyl-prolyl-cis-trans-isomera se FKBP in which this pocket is involved in the binding of the macrocy clic compound FK506 (refs 8-11).