6CBJ

Crystal Structure of DH270.3 Fab in complex with Man9

Summary for 6CBJ

• Entry DOI: 10.2210/pdb6cbj/pdb
• Related: 5TPL
• Descriptor: DH270.3 Fab heavy chain, DH270.3 Fab light chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: fab fragment, hiv-1, antibody, glycan, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 50529.78

Authors

Fera, D.,Harrison, S.C. (deposition date: 2018-02-03, release date: 2018-02-21, Last modification date: 2024-10-23)

Primary citation

Fera, D.,Lee, M.S.,Wiehe, K.,Meyerhoff, R.R.,Piai, A.,Bonsignori, M.,Aussedat, B.,Walkowicz, W.E.,Ton, T.,Zhou, J.O.,Danishefsky, S.,Haynes, B.F.,Harrison, S.C.
HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope.
Nat Commun, 9:1111-1111, 2018

PubMed Abstract: HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs-the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.

PubMed: 29549260
DOI: 10.1038/s41467-018-03565-6

Experimental method

X-RAY DIFFRACTION (2.85 Å)