1zls
From Proteopedia
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FAB 2G12 + Man4
Overview
Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a, conserved cluster of oligomannoses on the viral envelope glycoprotein, gp120, is a high priority in HIV vaccine design. A prior crystal structure, of 2G12 in complex with Man(9)GlcNAc(2) highlighted the central importance, of the D1 arm in antibody binding. To characterize the specificity of 2G12, more precisely, we performed solution-phase ELISA, carbohydrate microarray, analysis, and cocrystallized Fab 2G12 with four different oligomannose, derivatives (Man(4), Man(5), Man(7), and Man(8)) that compete with gp120, for binding to 2G12. Our combined studies reveal that 2G12 is capable of, binding both the D1 and D3 arms of the Man(9)GlcNAc(2) moiety, which would, provide more flexibility to make the required multivalent interactions, between the antibody and the gp120 oligomannose cluster than thought, previously. These results have important consequences for the design of, immunogens to elicit 2G12-like neutralizing antibodies as a component of, an HIV vaccine.
About this Structure
1ZLS is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12., Calarese DA, Lee HK, Huang CY, Best MD, Astronomo RD, Stanfield RL, Katinger H, Burton DR, Wong CH, Wilson IA, Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13372-7. Epub 2005 Sep 7. PMID:16174734
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