Structural highlights
Publication Abstract from PubMed
Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01-gp120 revealed that a four-residue insertion in CDRH3 contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46(G54W), a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46-gp120 structure, these results indicate that gp120 inner domain/bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.
Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design.,Diskin R, Scheid JF, Marcovecchio PM, West AP Jr, Klein F, Gao H, Gnanapragasam PN, Abadir A, Seaman MS, Nussenzweig MC, Bjorkman PJ Science. 2011 Oct 27. PMID:22033520[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Diskin R, Scheid JF, Marcovecchio PM, West AP Jr, Klein F, Gao H, Gnanapragasam PN, Abadir A, Seaman MS, Nussenzweig MC, Bjorkman PJ. Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design. Science. 2011 Oct 27. PMID:22033520 doi:10.1126/science.1213782
