Role of the major homology region in assembly of HIV-1 Gag

Biochemistry
P ProviteraSuzanne Scarlata

Abstract

The major homology region (MHR) is a highly conserved sequence in the gag gene of all retroviruses, including HIV-1. Its role in assembly is unknown, but deletion of the motif significantly impairs membrane binding and viral particle formation. To begin characterizing this defect, we have determined the contribution of this region to the energetics of the assembly process. Intrinsic fluorescence studies were conducted to determine the change in free energy associated with membrane and RNA binding using tRNA and large unilamellar vesicles of 1-palmitoyl-2-oleoylphosphatidylserine as models. For the wild-type protein, the change in free energy was within RT [600 cal/(mol.K)] whether Gag binds first to RNA or to the membrane. Thus, the initial binding of Gag can be to either substrate, but in vivo conditions favor initial association to RNA presumably due to its higher local concentration. After establishing the pattern of assembly, we compared the binding energy of Gag(WT) versus the deletion mutant, Gag(Delta)(MHR). Gag(WT) bound to membranes with a 2-fold higher affinity than Gag(Delta)(MHR), and the binding to RNA was similar for the two proteins. Gag prebound to RNA or to membrane exhibited approximately 2-4-fold greater bind...Continue Reading

Citations

Aug 23, 2003·Biophysical Chemistry·Marjorie Bon HommeSuzanne Scarlata
Apr 20, 2007·Journal of Virology·Liza S Z LarsenSuzanne Sandmeyer
Sep 8, 2007·The Journal of Clinical Investigation·Aleksandra LeligdowiczSarah Rowland-Jones
May 29, 2007·Journal of Molecular Biology·Yu-Fen ChangChin-Tien Wang
Sep 27, 2005·Biophysical Chemistry·Paxton ProviteraS Scarlata
Jul 23, 2003·Biochimica Et Biophysica Acta·Suzanne Scarlata, Carol Carter
Mar 1, 2005·The Journal of Biological Chemistry·Doug HusebyEric Barklis
Mar 18, 2004·Reviews in Medical Virology·Catherine S Adamson, Ian M Jones
Jun 24, 2017·Archives of Virology·Saki KokawaTetsuya Mizutani
Feb 5, 2021·Journal of Molecular Biology·Yisong DengJames R Williamson

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