3U7W

Crystal structure of NIH45-46 Fab

Summary for 3U7W

• Entry DOI: 10.2210/pdb3u7w/pdb
• Related: 3U7Y
• Descriptor: Heavy chain, Ig gamma-1 chain C region, Light chain, Ig kappa chain C region, GLYCEROL, ... (6 entities in total)
• Functional Keywords: ig fold, antibody, hiv gp120, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 48683.33

Authors

Diskin, R.,Bjorkman, P.J. (deposition date: 2011-10-14, release date: 2011-11-16, Last modification date: 2023-09-13)

Primary citation

Diskin, R.,Scheid, J.F.,Marcovecchio, P.M.,West, A.P.,Klein, F.,Gao, H.,Gnanapragasam, P.N.,Abadir, A.,Seaman, M.S.,Nussenzweig, M.C.,Bjorkman, P.J.
Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design.
Science, 334:1289-1293, 2011

PubMed Abstract: 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 heavy chain complementarity-determining region 3 (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 and bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.

PubMed: 22033520
DOI: 10.1126/science.1213782

Experimental method

X-RAY DIFFRACTION (2.6 Å)