5BZW

Crystal Structure of PCDN-27B, an antibody from the PCDN family of HIV-1 antibodies

Summary for 5BZW

• Entry DOI: 10.2210/pdb5bzw/pdb
• Related: 5BZD
• Descriptor: 2B3 HIV Antibody light chain, 2B3 HIV Antibody heavy chain, SULFATE ION, ... (5 entities in total)
• Functional Keywords: hiv, antibody, fab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 49129.56

Authors

Garces, F.,WILSON, I.A. (deposition date: 2015-06-11, release date: 2016-05-25, Last modification date: 2023-09-27)

Primary citation

MacLeod, D.T.,Choi, N.M.,Briney, B.,Garces, F.,Ver, L.S.,Landais, E.,Murrell, B.,Wrin, T.,Kilembe, W.,Liang, C.H.,Ramos, A.,Bian, C.B.,Wickramasinghe, L.,Kong, L.,Eren, K.,Wu, C.Y.,Wong, C.H.,Kosakovsky Pond, S.L.,Wilson, I.A.,Burton, D.R.,Poignard, P.
Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch.
Immunity, 44:1215-1226, 2016

PubMed Abstract: The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only ∼11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.

PubMed: 27192579
DOI: 10.1016/j.immuni.2016.04.016

Experimental method

X-RAY DIFFRACTION (2.9 Å)