CRYSTAL-STRUCTURE OF THE DBL AND PLECKSTRIN HOMOLOGY DOMAINS FROM THEHUMAN SON OF SEVENLESS PROTEIN

Proteins containing Dbl homology (DH) domains activate Rho-family GTPa ses by functioning as specific guanine nucleotide exchange factors. Al l known DH domains have associated C-terminal pleckstrin homology (PH) domains that are implicated in targeting and regulatory functions. Th e crystal structure of a fragment of the human Son of sevenless protei n containing the DH and PH domains has been determined at 2.3 Angstrom resolution. The entirely alpha-helical DH domain is unrelated in arch itecture to other nucleotide exchange factors. The active site of the DH domain, identified on the basis of sequence conservation and struct ural features, lies near the interface between the DH and PH domains. The structure suggests that ligation of the PH domain will be coupled structurally to the GTPase binding site.