1W72

Crystal structure of HLA-A1:MAGE-A1 in complex with Fab-Hyb3

Summary for 1W72

• Entry DOI: 10.2210/pdb1w72/pdb
• Related: 1AO7 1BD2 1FO0 1G6R 1MWA 1OGA 2CKB
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, BETA-2-MICROGLOBULIN, MELANOMA-ASSOCIATED ANTIGEN 1, ... (7 entities in total)
• Functional Keywords: immune system, hla/fab fragment, human leucocyte antigen, peptide-specific fab, tcr-like binding, mhc-i
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30443; Secreted: P61769; Cytoplasm: P43355
• Total number of polymer chains: 10
• Total formula weight: 182094.00

Authors

Hulsmeyer, M.,Chames, P.,Hillig, R.C.,Stanfield, R.L.,Held, G.,Coulie, P.G.,Alings, C.,Wille, G.,Saenger, W.,Uchanska-Ziegler, B.,Hoogenboom, H.R.,Ziegler, A. (deposition date: 2004-08-27, release date: 2004-11-09, Last modification date: 2024-10-16)

Primary citation

Hulsmeyer, M.,Chames, P.,Hillig, R.C.,Stanfield, R.L.,Held, G.,Coulie, P.G.,Alings, C.,Wille, G.,Saenger, W.,Uchanska-Ziegler, B.,Hoogenboom, H.R.,Ziegler, A.
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
J.Biol.Chem., 280:2972-, 2005

PubMed Abstract: 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.

PubMed: 15537658
DOI: 10.1074/JBC.M411323200

Experimental method

X-RAY DIFFRACTION (2.15 Å)