Mutation of the highly conserved Arg165 and Glu168 residues of human Gsalpha disrupts the alphaD-alphaE loop and enhances basal GDP/GTP exchange rate

Journal of Cellular Biochemistry
María Victoria HinrichsJuan Olate

Abstract

G protein signalling regulates a wide range of cellular processes such as motility, differentiation, secretion, neurotransmission, and cell division. G proteins consist of three subunits organized as a Galpha monomer associated with a Gbetagamma heterodimer. Structural studies have shown that Galpha subunits are constituted by two domains: a Ras-like domain, also called the GTPase domain (GTPaseD), and an helical domain (HD), which is unique to heterotrimeric G-proteins. The HD display significantly higher primary structure diversity than the GTPaseD. Regardless of this diversity, there are small regions of the HD which show high degree of identity with residues that are 100% conserved. One of such regions is the alpha helixD-alpha helixE loop (alphaD-alphaE) in the HD, which contains the consensus aminoacid sequence R*-[RSA]-[RSAN]-E*-[YF]-[QH]-L in all mammalian Galpha subunits. Interestingly, the highly conserved arginine (R*) and glutamic acid (E*) residues form a salt bridge that stabilizes the alphaD-alphaE loop, that is localized in the top of the cleft formed between the GTPaseD and HD. Because the guanine nucleotide binding site is deeply buried in this cleft and those interdomain interactions are playing an important ...Continue Reading

References

Apr 1, 1974·Analytical Biochemistry·Y SalomonM Rodbell
Jan 1, 1994·Methods in Enzymology·E LeeA G Gilman
Jan 25, 1996·Nature·D G LambrightP B Sigler
Jan 1, 1996·Annual Review of Pharmacology and Toxicology·R K SunaharaA G Gilman
Jan 1, 1997·Annual Review of Pharmacology and Toxicology·D E Clapham, E J Neer
Jan 1, 1997·Annual Review of Biochemistry·S R Sprang
Aug 1, 1997·Biochemical Pharmacology·J D Hildebrandt
Feb 14, 1998·Nature Structural Biology·N P Skiba, H E Hamm
Oct 28, 1998·Proceedings of the National Academy of Sciences of the United States of America·W Liu, J K Northup
Jun 8, 1999·The Journal of Biological Chemistry·D E Coleman, S R Sprang
Jun 3, 2000·Annual Review of Pharmacology and Toxicology·L De VriesM G Farquhar
Apr 6, 2001·The Journal of Biological Chemistry·E P MarinT P Sakmar
Sep 1, 2001·Molecular Cell Biology Research Communications : MCBRC·T O ThomasH E Hamm
Oct 12, 2001·Trends in Endocrinology and Metabolism : TEM·N Dascal
Mar 8, 2002·Cellular Signalling·Paul R Albert, Liliane Robillard
Apr 23, 2002·Journal of Cellular Biochemistry·Mónica BritoJuan Olate
Jan 9, 2003·Trends in Biochemical Sciences·Jacqueline Cherfils, Marc Chabre
Jul 17, 2003·Progress in Biophysics and Molecular Biology·Stefan Offermanns
Dec 13, 2003·Endocrine Reviews·Theresa M Cabrera-VeraHeidi E Hamm

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