Structures of three different pleckstrin homology domains have been determined within the past year. They have a common core consisting of a seven-stranded and strongly bent beta-sheet and a C-terminal alpha-helix that packs against the beta-sheet. Phosphatidylinositol 4,5-bisphosphate and related compounds specifically bind to pleckstrin homology domains, suggesting that the domain may be involved in reversible anchorage to membranes or in recognition of a second messenger, such as inositol 1,4,5-trisphosphate. Pleckstrin homology domains have also been suggested to bind to the G beta gamma complex, but direct evidence for this is missing.