SOLUTION STRUCTURE OF A PLECKSTRIN-HOMOLOGY DOMAIN

Pleckstrin(1), the major protein kinase C substrate of platelets, cont ains domains of about 100 amino acids at the amino and carboxy termini that have been found in a number of proteins, including serine/threon ine kinases, GTPase-activating proteins, phospholipases and cytoskelet al proteins(2-5). These conserved sequences, termed pleckstrin-homolog y (PH) domains, are thought to be involved in signal transduction. But the details of the function and binding partners of the PH domains ha ve not been characterized. Here we report the solution structure of th e N-terminal pleckstrin-homology domain of pleckstrin determined using heteronuclear three-dimensional nuclear magnetic resonance spectrosco py. The structure consists of an up-and-down beta-barrel of seven anti parallel beta-strands and a C-terminal amphiphilic alpha-helix that ca ps one end of the barrel. The overall topology of the domain is simila r to that of the retinol-binding protein family of structures(6-10).