5TE4

Crystal Structure of Broadly Neutralizing VRC01-class Antibody N6 in Complex with HIV-1 Clade G Strain X2088 gp120 Core

Summary for 5TE4

• Entry DOI: 10.2210/pdb5te4/pdb
• Related: 5TE6 5TE7
• Descriptor: HIV-1 clade G strain X2088 gp120, Heavy chain of antibody N6, Light chain of antibody N6, ... (8 entities in total)
• Functional Keywords: hiv-1, vrc01-class antibody, n6, cd4-binding site, gp120, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 91172.63

Authors

Zhou, T.,Kwong, P.D. (deposition date: 2016-09-20, release date: 2016-11-23, Last modification date: 2024-10-23)

Primary citation

Huang, J.,Kang, B.H.,Ishida, E.,Zhou, T.,Griesman, T.,Sheng, Z.,Wu, F.,Doria-Rose, N.A.,Zhang, B.,McKee, K.,O'Dell, S.,Chuang, G.Y.,Druz, A.,Georgiev, I.S.,Schramm, C.A.,Zheng, A.,Joyce, M.G.,Asokan, M.,Ransier, A.,Darko, S.,Migueles, S.A.,Bailer, R.T.,Louder, M.K.,Alam, S.M.,Parks, R.,Kelsoe, G.,Von Holle, T.,Haynes, B.F.,Douek, D.C.,Hirsch, V.,Seaman, M.S.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.,Connors, M.
Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth.
Immunity, 45:1108-1121, 2016

PubMed Abstract: Detailed studies of the broadly neutralizing antibodies (bNAbs) that underlie the best available examples of the humoral immune response to HIV are providing important information for the development of therapies and prophylaxis for HIV-1 infection. Here, we report a CD4-binding site (CD4bs) antibody, named N6, that potently neutralized 98% of HIV-1 isolates, including 16 of 20 that were resistant to other members of its class. N6 evolved a mode of recognition such that its binding was not impacted by the loss of individual contacts across the immunoglobulin heavy chain. In addition, structural analysis revealed that the orientation of N6 permitted it to avoid steric clashes with glycans, which is a common mechanism of resistance. Thus, an HIV-1-specific bNAb can achieve potent, near-pan neutralization of HIV-1, making it an attractive candidate for use in therapy and prophylaxis.

PubMed: 27851912
DOI: 10.1016/j.immuni.2016.10.027

Experimental method

X-RAY DIFFRACTION (2.75 Å)