4RNR

Crystal structure of broadly neutralizing anti-HIV antibody PGT130

Summary for 4RNR

• Entry DOI: 10.2210/pdb4rnr/pdb
• Descriptor: PGT130 Heavy Chain, PGT130 Light Chain, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: pgt130, pgt 130, immunoglobulin fold, broadly neutralizing antibody, hiv-1 gp120 binding, n-linked glycan, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 97082.40

Authors

Kong, L.,Wilson, I.A. (deposition date: 2014-10-24, release date: 2014-11-19, Last modification date: 2024-10-16)

Primary citation

Doores, K.J.,Kong, L.,Krumm, S.A.,Le, K.M.,Sok, D.,Laserson, U.,Garces, F.,Poignard, P.,Wilson, I.A.,Burton, D.R.
Two Classes of Broadly Neutralizing Antibodies within a Single Lineage Directed to the High-Mannose Patch of HIV Envelope.
J.Virol., 89:1105-1118, 2015

PubMed Abstract: The high-mannose patch of human immunodeficiency virus (HIV) envelope (Env) elicits broadly neutralizing antibodies (bnAbs) during natural infection relatively frequently, and consequently, this region has become a major target of vaccine design. However, it has also become clear that antibody recognition of the region is complex due, at least in part, to variability in neighboring loops and glycans critical to the epitopes. bnAbs against this region have some shared features and some distinguishing features that are crucial to understand in order to design optimal immunogens that can induce different classes of bnAbs against this region. Here, we compare two branches of a single antibody lineage, in which all members recognize the high-mannose patch. One branch (prototype bnAb PGT128) has a 6-amino-acid insertion in CDRH2 that is crucial for broad neutralization. Antibodies in this branch appear to favor a glycan site at N332 on gp120, and somatic hypermutation is required to accommodate the neighboring V1 loop glycans and glycan heterogeneity. The other branch (prototype bnAb PGT130) lacks the CDRH2 insertion. Antibodies in this branch are noticeably effective at neutralizing viruses with an alternate N334 glycan site but are less able to accommodate glycan heterogeneity. We identify a new somatic variant within this branch that is predominantly dependent on N334. The crystal structure of PGT130 offers insight into differences from PGT128. We conclude that different immunogens may be required to elicit bnAbs that have the optimal characteristics of the two branches of the lineage described.

PubMed: 25378488
DOI: 10.1128/JVI.02905-14

Experimental method

X-RAY DIFFRACTION (2.758 Å)