Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans.
Journal, issue, pages	PLoS Pathog, Vol. 9, Issue 5, Page e1003342, Year 2013
Publish date	May 2, 2013
Authors	Jean-Philippe Julien / Devin Sok / Reza Khayat / Jeong Hyun Lee / Katie J Doores / Laura M Walker / Alejandra Ramos / Devan C Diwanji / Robert Pejchal / Albert Cupo / Umesh Katpally / Rafael S Depetris / Robyn L Stanfield / Ryan McBride / Andre J Marozsan / James C Paulson / Rogier W Sanders / John P Moore / Dennis R Burton / Pascal Poignard / Andrew B Ward / Ian A Wilson /
PubMed Abstract	New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, ...New broad and potent neutralizing HIV-1 antibodies have recently been described that are largely dependent on the gp120 N332 glycan for Env recognition. Members of the PGT121 family of antibodies, isolated from an African donor, neutralize ∼70% of circulating isolates with a median IC50 less than 0.05 µg ml(-1). Here, we show that three family members, PGT121, PGT122 and PGT123, have very similar crystal structures. A long 24-residue HCDR3 divides the antibody binding site into two functional surfaces, consisting of an open face, formed by the heavy chain CDRs, and an elongated face, formed by LCDR1, LCDR3 and the tip of the HCDR3. Alanine scanning mutagenesis of the antibody paratope reveals a crucial role in neutralization for residues on the elongated face, whereas the open face, which accommodates a complex biantennary glycan in the PGT121 structure, appears to play a more secondary role. Negative-stain EM reconstructions of an engineered recombinant Env gp140 trimer (SOSIP.664) reveal that PGT122 interacts with the gp120 outer domain at a more vertical angle with respect to the top surface of the spike than the previously characterized antibody PGT128, which is also dependent on the N332 glycan. We then used ITC and FACS to demonstrate that the PGT121 antibodies inhibit CD4 binding to gp120 despite the epitope being distal from the CD4 binding site. Together, these structural, functional and biophysical results suggest that the PGT121 antibodies may interfere with Env receptor engagement by an allosteric mechanism in which key structural elements, such as the V3 base, the N332 oligomannose glycan and surrounding glycans, including a putative V1/V2 complex biantennary glycan, are conformationally constrained.
External links	PLoS Pathog / PubMed:23658524 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	1.75 - 14.0 Å
Structure data	EMDB-5624: Broadly Neutralizing Antibody PGT121 Allosterically Modulates CD4 Binding via Recognition of the HIV-1 gp120 V3 Base and Multiple Surrounding Glycans Method: EM (single particle) / Resolution: 14.0 Å PDB-4jy4: Crystal structure of human Fab PGT121, a broadly reactive and potent HIV-1 neutralizing antibody Method: X-RAY DIFFRACTION / Resolution: 2.8 Å PDB-4jy5: Crystal structure of human Fab PGT122, a broadly reactive and potent HIV-1 neutralizing antibody Method: X-RAY DIFFRACTION / Resolution: 1.75 Å PDB-4jy6: Crystal structure of human Fab PGT123, a broadly reactive and potent HIV-1 neutralizing antibody Method: X-RAY DIFFRACTION / Resolution: 2.5 Å
Chemicals	ChemComp-GOL: GLYCEROL / Glycerol ChemComp-HOH: WATER / Water ChemComp-ZN: Unknown entry
Source	Human immunodeficiency virus 1 homo sapiens (human)
Keywords	IMMUNE SYSTEM / Broadly neutralizing antibody against HIV-1 / HIV-1 Env gp120 subunit