Crystal structure of broadly neutralizing anti-hiv-1 antibody ch103Crystal structure of broadly neutralizing anti-hiv-1 antibody ch103

Structural highlights

4jam is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.

Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.,Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L, Becker J, Benjamin B, Blakesley R, Bouffard G, Brooks S, Coleman H, Dekhtyar M, Gregory M, Guan X, Gupta J, Han J, Hargrove A, Ho SL, Johnson T, Legaspi R, Lovett S, Maduro Q, Masiello C, Maskeri B, McDowell J, Montemayor C, Mullikin J, Park M, Riebow N, Schandler K, Schmidt B, Sison C, Stantripop M, Thomas J, Thomas P, Vemulapalli M, Young A, Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF Nature. 2013 Apr 3. doi: 10.1038/nature12053. PMID:23552890[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Liao HX, Lynch R, Zhou T, Gao F, Alam SM, Boyd SD, Fire AZ, Roskin KM, Schramm CA, Zhang Z, Zhu J, Shapiro L, Becker J, Benjamin B, Blakesley R, Bouffard G, Brooks S, Coleman H, Dekhtyar M, Gregory M, Guan X, Gupta J, Han J, Hargrove A, Ho SL, Johnson T, Legaspi R, Lovett S, Maduro Q, Masiello C, Maskeri B, McDowell J, Montemayor C, Mullikin J, Park M, Riebow N, Schandler K, Schmidt B, Sison C, Stantripop M, Thomas J, Thomas P, Vemulapalli M, Young A, Mullikin JC, Gnanakaran S, Hraber P, Wiehe K, Kelsoe G, Yang G, Xia SM, Montefiori DC, Parks R, Lloyd KE, Scearce RM, Soderberg KA, Cohen M, Kamanga G, Louder MK, Tran LM, Chen Y, Cai F, Chen S, Moquin S, Du X, Joyce MG, Srivatsan S, Zhang B, Zheng A, Shaw GM, Hahn BH, Kepler TB, Korber BT, Kwong PD, Mascola JR, Haynes BF. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 3. doi: 10.1038/nature12053. PMID:23552890 doi:10.1038/nature12053

4jam, resolution 1.65Å

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