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G Protein‐Coupled Receptor Kinase 4γ (GRK4γ) Interacts with the Alpha Helical Domain of Gα s
Author(s) -
Andresen Bradley T.,
Sisk Kay,
Keever Lindsay B.,
Bastepe Murat,
Jackson Edwin K.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.944.1
Subject(s) - helix (gastropod) , turn (biochemistry) , coiled coil , biology , chemistry , microbiology and biotechnology , biochemistry , ecology , snail
GRK4γ is constitutively active, and polymorphisms of GRK4γ are linked to clinical hypertension and can induce experimental hypertension. Recent studies demonstrate that GRK4γ interacts with inactive Gα s without interfering with the G βγ complex. To better understand this interaction and GRK4γ function, we investigated the site of interaction between Gα s and GRK4γ utilizing chimeric Gα s/q and Gα s/i1 subunits (only Gα s and Gα 13 interact with GRK4γ). Chimeric Gα s/q suggested that GRK4γ interacts with the amino‐terminal portion of Gα s , which was confirmed with the chimeric Gα s/i1 . These data indicate that GRK4γ interacts with amino acids 60 ‐ 138 in the helical domain of Gα s . Sequence alignment between the Gα subunits suggested 3 specific points of interaction in the αB helix (Q111, D115, and S119), but after site directed mutagenesis GRK4γ still bound to Gα s . Therefore, the interaction involves multiple amino acids. Since the structure of the helical domain of Gα s that interacts with GRK4γ resembles a hook, much of the helical domain may be involved in interacting with GRK4γ. Binding to the alpha helical domain of Gα s explains how GRK4γ can bind to inactive Gα s and not displace Gβγ as well as account for its constitutive activity. Support was provided by American Health Assistance Foundation and Department of Veterans affairs VISN 15.