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A phosphoinositide‐binding sequence is shared by PH domain target molecules—a model for the binding of PH domains to proteins
Author(s) -
Alberti Saverio
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19980401)31:1<1::aid-prot1>3.0.co;2-r
Subject(s) - pleckstrin homology domain , pdz domain , binding site , phosphotyrosine binding domain , binding domain , plasma protein binding , peptide sequence , sequence (biology) , homology modeling , biophysics , biology , chemistry , biochemistry , membrane , signal transduction , gene , enzyme , sh2 domain , receptor tyrosine kinase
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 β , 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 β strand–β 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. © 1998 Wiley‐Liss, Inc.