6MZJ

Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 2 Fabs bound, sharpened map

Summary for 6MZJ

• Entry DOI: 10.2210/pdb6mzj/pdb
• EMDB information: 9294 9295 9303 9304
• Descriptor: 426c DS-SOSIP D3, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: hiv envelope, germline vrc01 antibody, viral fusion protein, glycan shield, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 7
• Total formula weight: 340490.65

Authors

Borst, A.J.,Weidle, C.E.,Gray, M.D.,Frenz, B.,Snijder, J.,Joyce, M.G.,Georgiev, I.S.,Stewart-Jones, G.B.E.,Kwong, P.D.,McGuire, A.T.,DiMaio, F.,Stamatatos, L.,Pancera, M.,Veesler, D. (deposition date: 2018-11-05, release date: 2018-11-14, Last modification date: 2024-11-13)

Primary citation

Borst, A.J.,Weidle, C.E.,Gray, M.D.,Frenz, B.,Snijder, J.,Joyce, M.G.,Georgiev, I.S.,Stewart-Jones, G.B.,Kwong, P.D.,McGuire, A.T.,DiMaio, F.,Stamatatos, L.,Pancera, M.,Veesler, D.
Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core.
Elife, 7:-, 2018

PubMed Abstract: VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design.

PubMed: 30403372
DOI: 10.7554/eLife.37688

Experimental method

ELECTRON MICROSCOPY (4.8 Å)