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HIKE, a candidate protein binding site for PH domains, is a major regulatory region of G β proteins
Author(s) -
Alberti Saverio
Publication year - 1999
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(19990515)35:3<360::aid-prot10>3.0.co;2-j
Subject(s) - heterotrimeric g protein , ankyrin , g protein , adenylyl cyclase , binding site , microbiology and biotechnology , protein subunit , ankyrin repeat , chemistry , biochemistry , biology , signal transduction , gene
HIKE is a highly conserved sequence motif that selectively occurs in proteins candidate to bind PH domains, e.g., the β subunit of heterotrimeric G proteins, kinases, ankyrin and kinesin. Thus, the HIKE region has been predicted to be a protein docking site for PH domains. This work evidentiates recent experimental evidence that unambiguously defines the functional role of HIKE in G β as a multiple effector docking site and as a major regulatory region of G protein's function. Indeed, the G β HIKE interacts with the β‐adrenergic receptor kinase, G α , G γ , adenylyl cyclase 2, phospholipase C β2, inward rectifier K channels, calcium channel α1B, calmodulin, phosducin, ste20. Quite interestingly, HIKE is located in the G β region that faces the cell membrane. Thus, HIKE also interacts with the cell membrane and may dynamically regulate membrane vs effector binding of the G αβγ trimer. These findings fulfill a major prediction of the HIKE model, i.e., that HIKE is a regulatory region for protein‐protein interactions. A role of HIKE as a proteic binding site for PH domains is supported by the profound influence of HIKE mutations on the largely PH‐mediated binding of β‐ARK to G β . Proteins 1999;35:360–363. © 1999 Wiley‐Liss, Inc.