A phosphoinositide-binding sequence is shared by PH domain target molecules—a model for the binding of PH domains to proteins

✍ Scribed by Saverio Alberti

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 326 KB
• Volume: 31
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(19980401)31:1<1::aid-prot1>3.0.co;2-r

✦ Synopsis

Pleckstrin homology (PH) domains have been proven to bind phosphoinositides (PI) and inositolphosphates (IP). On the other hand, a binding of PH domains to proteins is still a matter of debate. The goal of this work was to identify potential PH domain protein target sites and to build a model for PH domain-protein binding. A candidate sequence, called HIKE, was identified by sequence homology analysis of the proteins that are considered the strongest PH binding candidates, i.e., G ␤ , PKC, and Akt. HIKE contains a PI binding sequence and fulfills several criteria for a potential PH-binding site, i.e., it is present in other PH-binding candidates, lies in regulatory regions independently predicted to bind PH domains, and is conserved in 3-D structure among different molecules. These findings and the similarities with the mode of binding of PTB and PDZ domains suggest a ␤ strand-␤ strand coordination model for PH-protein binding. The HIKE model predicts that membrane anchoring of PH domains and their targets could be a critical step in their interaction, which would consistently explain why PH-protein binding has only been detected in the presence of PI. Proteins 31:1-9, 1998.