B Zhang

CA Bewley

DR Burton

JS McLellan

M Pancera

N Doria-Rose

PD Kwong

S Shahzad-ul-Hussan

WC Koff

Y Yang

Retrovirology

English

Crossref

POSTER PRESENTATION Open AccessStructural comparison of somatically related PG9and PG16 in complex with their epitope revealsdifferences in glycan recognitionM Pancera*, JS McLellan, S Shahzad-ul-Hussan, N Doria-Rose, B Zhang, Y Yang, DR Burton, WC Koff, CA Bewley,PD KwongFrom AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundThe somatically related antibodies, PG9 and PG16, neutra-lize 70-80% of HIV-1 isolates and bind a glycosylated epi-tope in the V1/V2 domain of HIV-1 gp120. Mutations inV1/V2, and sometimes V3 depending on the HIV-1 strain,affect neutralization and a glycan on Asn160 is requiredfor neutralization. Both antibodies also preferentially bindthe native trimer over monomeric gp120, especially PG16.The structure of PG9 in complex with its epitope, a scaf-folded V1/V2 from HIV-1 strain ZM109, was recentlysolved and showed that PG9 targets a site of vulnerabilitycomprising 2 glycans and a b-strand.MethodsTo understand the differences in binding properties fromthese two somatically related antibodies, we first assessedtheir binding to monomeric gp120 and scaffolded V1/V2proteins with different glycan types (oligomannose, hybrid,and complex). In order for PG16 to bind the scaffoldedV1/V2, the protein had to be expressed in mammaliancells in the presence of swainsonine, which inhibits glycanmaturation past the hybrid state. A stable complex couldbe obtained between PG16 and a scaffolded V1/V2domain from ZM109, and this complex was crystallized.ResultsAlthough the structure of PG16 bound to scaffolded V1/V2 resembled that of PG9, some differences were seen: 1)PG16 binding to the b-strand is weaker than PG9 withfewer charged interactions, 2) PG16 interacts with a hybridglycan at position N173. The difference in binding recog-nition of PG9 and PG16 to monomeric gp120 depends onthe type of glycans present. PG16 binds the protein por-tion of V1/V2 weaker than PG9 and this might explain thehigher affinity of PG9 for the monomer. PG16 has evolveda second glycan site to compensate for weaker peptideinteraction.ConclusionThe results show the importance of polyclonal responsein infected individual to combat HIV-1, and in this case,to differential glycosylation.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-P74Cite this article as: Pancera et al.: Structural comparison of somaticallyrelated PG9 and PG16 in complex with their epitope reveals differencesin glycan recognition. Retrovirology 2012 9(Suppl 2):P74.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitNIH/NIAID/VRC, Bethesda, MD, USAPancera et al. Retrovirology 2012, 9(Suppl 2):P74http://www.retrovirology.com/content/9/S2/P74© 2012 Pancera et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Structural comparison of somatically related PG9 and PG16 in complex with their epitope reveals differences in glycan recognition

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Structural comparison of somatically related PG9 and PG16 in complex with their epitope reveals differences in glycan recognition

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