1e6o
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CRYSTAL STRUCTURE OF FAB13B5 AGAINST HIV-1 CAPSID PROTEIN P24
OverviewOverview
BACKGROUND: Elucidating the structural basis of antigen-antibody, recognition ideally requires a structural comparison of free and complexed, components. To this end we have studied a mouse monoclonal antibody, denoted 13B5, raised against p24, the capsid protein of HIV-1. We have, previously described the first crystal structure of intact p24 as, visualized in the Fab13B5-p24 complex. Here we report the structure of the, uncomplexed Fab13B5 at 1.8 A resolution and analyze the Fab-p24 interface, and the conformational changes occurring upon complex formation. RESULTS:, Fab13B5 recognizes a nearly continuous epitope comprising a, helix-turn-helix motif in the C-terminal domain of p24. Only 4, complementarity-determining regions (CDRs) are in contact with p24 with, most interactions being by the heavy chain. Comparison of the free and, complexed Fab reveals that structural changes upon binding are localized, to a few side chains of CDR-H1 and -H2 but involve a larger, concerted, displacement of CDR-H3. Antigen binding is also associated with an 8, degrees relative rotation of the heavy and light chain variable regions., In p24, small conformational changes localized to the turn between the two, helices comprising the epitope result from Fab binding. CONCLUSIONS: The, relatively small area of contact between Fab13B5 and p24 may be related to, the fact that the epitope is a continuous peptide rather than a more, complex protein surface and correlates with a relatively low affinity of, antigen and antibody. Despite this, a significant quaternary structural, change occurs in the Fab upon complex formation, with additional smaller, adaptations of both antigen and antibody.
About this StructureAbout this Structure
1E6O is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Mutual conformational adaptations in antigen and antibody upon complex formation between an Fab and HIV-1 capsid protein p24., Monaco-Malbet S, Berthet-Colominas C, Novelli A, Battai N, Piga N, Cheynet V, Mallet F, Cusack S, Structure. 2000 Oct 15;8(10):1069-77. PMID:11080628
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