5ESZ

Crystal Structure of Broadly Neutralizing Antibody CH04, Isolated from Donor CH0219, in Complex with Scaffolded Trimeric HIV-1 Env V1V2 Domain from the Clade AE Strain A244

Summary for 5ESZ

• Entry DOI: 10.2210/pdb5esz/pdb
• Descriptor: CH04 Heavy Chain, CH04 Light Chain, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase,Envelope glycoprotein gp160, ... (8 entities in total)
• Functional Keywords: hiv-1, env, v1v2, ch0219, chavi, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 153403.10

Authors

Gorman, J.,Yang, M.,Kwong, P.D. (deposition date: 2015-11-17, release date: 2015-12-16, Last modification date: 2024-10-30)

Primary citation

Gorman, J.,Soto, C.,Yang, M.M.,Davenport, T.M.,Guttman, M.,Bailer, R.T.,Chambers, M.,Chuang, G.Y.,DeKosky, B.J.,Doria-Rose, N.A.,Druz, A.,Ernandes, M.J.,Georgiev, I.S.,Jarosinski, M.C.,Joyce, M.G.,Lemmin, T.M.,Leung, S.,Louder, M.K.,McDaniel, J.R.,Narpala, S.,Pancera, M.,Stuckey, J.,Wu, X.,Yang, Y.,Zhang, B.,Zhou, T.,Mullikin, J.C.,Baxa, U.,Georgiou, G.,McDermott, A.B.,Bonsignori, M.,Haynes, B.F.,Moore, P.L.,Morris, L.,Lee, K.K.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design.
Nat. Struct. Mol. Biol., 23:81-90, 2016

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 Env V1V2 arise in multiple donors. However, atomic-level interactions had previously been determined only with antibodies from a single donor, thus making commonalities in recognition uncertain. Here we report the cocrystal structure of V1V2 with antibody CH03 from a second donor and model Env interactions of antibody CAP256-VRC26 from a third donor. These V1V2-directed bNAbs used strand-strand interactions between a protruding antibody loop and a V1V2 strand but differed in their N-glycan recognition. Ontogeny analysis indicated that protruding loops develop early, and glycan interactions mature over time. Altogether, the multidonor information suggested that V1V2-directed bNAbs form an 'extended class', for which we engineered ontogeny-specific antigens: Env trimers with chimeric V1V2s that interacted with inferred ancestor and intermediate antibodies. The ontogeny-based design of vaccine antigens described here may provide a general means for eliciting antibodies of a desired class.

PubMed: 26689967
DOI: 10.1038/nsmb.3144

Experimental method

X-RAY DIFFRACTION (4.191 Å)