1w72: Difference between revisions

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CRYSTAL STRUCTURE OF HLA-A1:MAGE-A1 IN COMPLEX WITH FAB-HYB3

OverviewOverview

Antibodies with T cell receptor-like specificity possess a considerable, diagnostic and therapeutic potential, but the structural basis of the, interaction between an antibody and an histocompatibility antigen has so, far not been determined. We present here the crystal structure (at 2.15 A, resolution) of the recombinant, affinity-matured human antibody fragment, Fab-Hyb3 bound to the tumor-associated human leukocyte antigen, (HLA)/peptide complex HLA-A1.MAGE-A1. Fab-Hyb3 employs a diagonal docking, mode resembling that of T cell receptors. However, other than these, natural ligands, the antibody uses only four of its six, complementarity-determining regions for direct interactions with the, target. It recognizes the C-terminal half of the MAGE-A1 peptide, the, HLA-A1 alpha1-helix, and N-terminal residues of the alpha2-helix, accompanied by a large tilting angle between the two types of molecules, within the complex. Interestingly, only a single hydrogen bond between a, peptide side chain and Fab-Hyb3 contributes to the interaction, but large, buried surface areas with pronounced shape complementarity assure high, affinity and specificity for MAGE-A1. The HLA-A1.MAGE-A1.antibody, structure is discussed in comparison with those of natural ligands, recognizing HLA.peptide complexes.

About this StructureAbout this Structure

1W72 is a Protein complex structure of sequences from Homo sapiens with GOL as ligand. Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

A major histocompatibility complex-peptide-restricted antibody and t cell receptor molecules recognize their target by distinct binding modes: crystal structure of human leukocyte antigen (HLA)-A1-MAGE-A1 in complex with FAB-HYB3., Hulsmeyer M, Chames P, Hillig RC, Stanfield RL, Held G, Coulie PG, Alings C, Wille G, Saenger W, Uchanska-Ziegler B, Hoogenboom HR, Ziegler A, J Biol Chem. 2005 Jan 28;280(4):2972-80. Epub 2004 Nov 10. PMID:15537658

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	[[Category: tcr-like binding]]		[[Category: tcr-like binding]]

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