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1w72
From Proteopedia
| 1w72, resolution 2.15Å () | |||||||||
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| Sites: | , , and | ||||||||
| Ligands: | |||||||||
| Related: | 1oga, 1ao7, 2ckb, 1bd2, 1fo0, 1mwa, 1g6r | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Contents |
CRYSTAL STRUCTURE OF HLA-A1:MAGE-A1 IN COMPLEX WITH FAB-HYB3
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1w72 is a 10 chain structure of Beta-2 microglobulin and Major histocompatibility complex with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See Also
Reference
- 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. 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. 2005 Jan 28;280(4):2972-80. Epub 2004 Nov 10. PMID:15537658 doi:10.1074/jbc.M411323200
- Chames P, Hufton SE, Coulie PG, Uchanska-Ziegler B, Hoogenboom HR. Direct selection of a human antibody fragment directed against the tumor T-cell epitope HLA-A1-MAGE-A1 from a nonimmunized phage-Fab library. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7969-74. PMID:10884427
- Chames P, Willemsen RA, Rojas G, Dieckmann D, Rem L, Schuler G, Bolhuis RL, Hoogenboom HR. TCR-like human antibodies expressed on human CTLs mediate antibody affinity-dependent cytolytic activity. J Immunol. 2002 Jul 15;169(2):1110-8. PMID:12097420
Categories: Homo sapiens | Alings, C. | Chames, P. | Coulie, P G. | Held, G. | Hillig, R C. | Hoogenboom, H R. | Hulsmeyer, M. | Saenger, W. | Stanfield, R L. | Uchanska-Ziegler, B. | Wille, G. | Ziegler, A. | Hla/fab fragment | Human leucocyte antigen | Immune system | Mhc-i | Peptide-specific fab | Tcr-like binding
