7kde

From Proteopedia

BG505 SOSIP.664 in complex with the V3-targeting rhesus macaque antibody 1485 and human gp120-gp41 interface antibody 8ANC195

Structural highlights

7kde is a 18 chain structure with sequence from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.55Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

Q2N0S6_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 PubMed

A small fraction of HIV-1- infected humans develop broadly neutralizing antibodies (bNAbs) against HIV-1 that protect macaques from simian immunodeficiency HIV chimeric virus (SHIV). Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Here, we report on a monoclonal antibody, Ab1485, isolated from a macaque infected with SHIVAD8 that developed broadly neutralizing serologic activity targeting the V3-glycan region of HIV-1 Env. Ab1485 neutralizes 38.1% of HIV-1 isolates in a 42-pseudovirus panel with a geometric mean IC50 of 0.055 microg/mLl and SHIVAD8 with an IC50 of 0.028 microg/mLl. Ab1485 binds the V3-glycan epitope in a glycan-dependent manner. A 3.5 A cryo-electron microscopy structure of Ab1485 in complex with a native-like SOSIP Env trimer showed conserved contacts with the N332gp120 glycan and gp120 GDIR peptide motif, but in a distinct Env-binding orientation relative to human V3/N332gp120 glycan-targeting bNAbs. Intravenous infusion of Ab1485 protected macaques from a high dose challenge with SHIVAD8. We conclude that macaques can develop bNAbs against the V3-glycan patch that resemble human V3-glycan bNAbs.

A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch.,Wang Z, Barnes CO, Gautam R, Cetrulo Lorenzi JC, Mayer CT, Oliveira TY, Ramos V, Cipolla M, Gordon KM, Gristick HB, West AP, Nishimura Y, Raina H, Seaman MS, Gazumyan A, Martin M, Bjorkman PJ, Nussenzweig MC, Escolano A Elife. 2020 Oct 21;9:e61991. doi: 10.7554/eLife.61991. PMID:33084569^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang Z, Barnes CO, Gautam R, Cetrulo Lorenzi JC, Mayer CT, Oliveira TY, Ramos V, Cipolla M, Gordon KM, Gristick HB, West AP, Nishimura Y, Raina H, Seaman MS, Gazumyan A, Martin M, Bjorkman PJ, Nussenzweig MC, Escolano A. A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch. Elife. 2020 Oct 21;9:e61991. PMID:33084569 doi:10.7554/eLife.61991