6mar | pdb_00006mar
HIV-1 Envelope Glycoprotein Clone BG505 delCT N332T in complex with broadly neutralizing antibody Fab PGT151
Structural highlights
FunctionQ2N0S6_9HIV1 The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990] Publication Abstract from PubMedAs the sole target of broadly neutralizing antibodies (bnAbs) to HIV, the envelope glycoprotein (Env) trimer is the focus of vaccination strategies designed to elicit protective bnAbs in humans. Because HIV Env is densely glycosylated with 75-90 N-glycans per trimer, most bnAbs use or accommodate them in their binding epitope, making the glycosylation of recombinant Env a key aspect of HIV vaccine design. Upon analysis of three HIV strains, we here find that site-specific glycosylation of Env from infectious virus closely matches Envs from corresponding recombinant membrane-bound trimers. However, viral Envs differ significantly from recombinant soluble, cleaved (SOSIP) Env trimers, strongly impacting antigenicity. These results provide a benchmark for virus Env glycosylation needed for the design of soluble Env trimers as part of an overall HIV vaccine strategy. Differential processing of HIV envelope glycans on the virus and soluble recombinant trimer.,Cao L, Pauthner M, Andrabi R, Rantalainen K, Berndsen Z, Diedrich JK, Menis S, Sok D, Bastidas R, Park SR, Delahunty CM, He L, Guenaga J, Wyatt RT, Schief WR, Ward AB, Yates JR 3rd, Burton DR, Paulson JC Nat Commun. 2018 Sep 12;9(1):3693. doi: 10.1038/s41467-018-06121-4. PMID:30209313[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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