A large subset of Pleckstrin Homology (PH) domains are immediately to the ('terminus of Diffuse B cell lyphoma (Dbl) Homology (DbH) domains. Db! domains are generally considered to be GTPase exchange factors; many are protooncogenes. PH domains appear to function as membrane recruitment factors, or have specific protein-protein interactions. Since dual domain (DbH/PH) constructs are known to have significant properties in other pathways, it is pos Mble that a defined interdomain relationship is required for DbH/PH function. We determined the solution structure of the human SOSl PH domain for a construct partially extended in to the preceeding DbH domain. There are spe cific structural contacts between the PH and the vestigial DbH domain. This appears to involve structural elements of this subfamily of PH domains, and of DbH domains. The hSOSl PH domain binds to inositol(l,4,5)triphosphate with a c. 60 /xM affinity. Using chemical shift titration, the binding site is identified to be essentially identical to that observed crystallographically for the IP3 complex with the PH domain of PLC<5. While the overall fold of the hSOSl PH domain is similar to other PH domains, the size and position of the intrastrand loops and the presence of an N terminal a helix of the vestigial DbH domain suggest that the subfamily of PH domains associated with DbH domains may be a well-defined structural group in which the PH domain is a membrane recruiter and modulator.
|Original language||English (US)|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Molecular Biology