id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-339796-gccnvh0z	Zhang, Si Min	Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins	2015-07-31		.txt	text/plain	9073	403	45	The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. Here we describe the roles of the Trp residues in the membrane-active MPER sequence in anti-HIV fusion inhibitor design and a surprising role in the biosynthesis of viral structural proteins.	./cache/cord-339796-gccnvh0z.txt	./txt/cord-339796-gccnvh0z.txt