6BF4

Crystal Structure of HIV-1 Clade AE Strain CNE55 gp120 Core in Complex with Neutralizing Antibody VRC-PG05 that Targets the Center of the Silent Face on the Outer Domain of gp120

Summary for 6BF4

• Entry DOI: 10.2210/pdb6bf4/pdb
• Descriptor: HIV-1 clade AE gp120 core, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-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, ... (14 entities in total)
• Functional Keywords: antibody, hiv-1, silent face, glycan, gp120, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 188011.69

Authors

Zhou, T.,Kwong, P.D. (deposition date: 2017-10-25, release date: 2018-03-07, Last modification date: 2023-10-04)

Primary citation

Zhou, T.,Zheng, A.,Baxa, U.,Chuang, G.Y.,Georgiev, I.S.,Kong, R.,O'Dell, S.,Shahzad-Ul-Hussan, S.,Shen, C.H.,Tsybovsky, Y.,Bailer, R.T.,Gift, S.K.,Louder, M.K.,McKee, K.,Rawi, R.,Stevenson, C.H.,Stewart-Jones, G.B.E.,Taft, J.D.,Waltari, E.,Yang, Y.,Zhang, B.,Shivatare, S.S.,Shivatare, V.S.,Lee, C.D.,Wu, C.Y.,Mullikin, J.C.,Bewley, C.A.,Burton, D.R.,Polonis, V.R.,Shapiro, L.,Wong, C.H.,Mascola, J.R.,Kwong, P.D.,Wu, X.
A Neutralizing Antibody Recognizing Primarily N-Linked Glycan Targets the Silent Face of the HIV Envelope.
Immunity, 48:500-513.e6, 2018

PubMed Abstract: Virtually the entire surface of the HIV-1-envelope trimer is recognized by neutralizing antibodies, except for a highly glycosylated region at the center of the "silent face" on the gp120 subunit. From an HIV-1-infected donor, #74, we identified antibody VRC-PG05, which neutralized 27% of HIV-1 strains. The crystal structure of the antigen-binding fragment of VRC-PG05 in complex with gp120 revealed an epitope comprised primarily of N-linked glycans from N262, N295, and N448 at the silent face center. Somatic hypermutation occurred preferentially at antibody residues that interacted with these glycans, suggesting somatic development of glycan recognition. Resistance to VRC-PG05 in donor #74 involved shifting of glycan-N448 to N446 or mutation of glycan-proximal residue E293. HIV-1 neutralization can thus be achieved at the silent face center by glycan-recognizing antibody; along with other known epitopes, the VRC-PG05 epitope completes coverage by neutralizing antibody of all major exposed regions of the prefusion closed trimer.

PubMed: 29548671
DOI: 10.1016/j.immuni.2018.02.013

Experimental method

X-RAY DIFFRACTION (2.382 Å)