3bo8
From Proteopedia
The High Resolution Crystal Structure of HLA-A1 Complexed with the MAGE-A1 Peptide
Structural highlights
Disease[B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.[1] Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Function[1A01_HUMAN] Involved in the presentation of foreign antigens to the immune system. [MAGA1_HUMAN] May be involved in transcriptional regulation through interaction with SNW1 and recruiting histone deactelyase HDAC1. May inhibit notch intracellular domain (NICD) transactivation. May play a role in embryonal development and tumor transformation or aspects of tumor progression. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.[15] [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAlthough there is X-ray crystallographic evidence that the interaction between major histocompatibility complex (MHC, in humans HLA) class I molecules and T cell receptors (TCR) or killer cell Ig-like receptors (KIR) may be accompanied by considerable changes in the conformation of selected residues or even entire loops within TCR or KIR, conformational changes between receptor-bound and -unbound MHC class I molecules of comparable magnitude have not been observed so far. We have previously determined the structure of the MHC class I molecule HLA-A1 bound to a melanoma antigen-encoding gene (MAGE)-A1-derived peptide in complex with a recombinant antibody fragment with TCR-like specificity, Fab-Hyb3. Here, we compare the X-ray structure of HLA-A1:MAGE-A1 with that complexed with Fab-Hyb3 to gain insight into structural changes of the MHC molecule that might be induced by the interaction with the antibody fragment. Apart from the expulsion of several water molecules from the interface, Fab-Hyb3 binding results in major rearrangements (up to 5.5 A) of heavy chain residues Arg65, Gln72, Arg145, and Lys146. Residue 65 is frequently and residues 72 and 146 are occasionally involved in TCR binding-induced conformational changes, as revealed by a comparison with MHC class I structures in TCR-liganded and -unliganded forms. On the other hand, residue 145 is subject to a reorientation following engagement of HLA-Cw4 and KIR2DL1. Therefore, conformational changes within the HLA-A1:MAGE-A1:Fab-Hyb3 complex include MHC residues that are also involved in reorientations in complexes with natural ligands, pointing to their central importance for the peptide-dependent recognition of MHC molecules. Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity.,Kumar P, Vahedi-Faridi A, Saenger W, Ziegler A, Uchanska-Ziegler B Protein Sci. 2009 Jan;18(1):37-49. PMID:19177349[16] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
Categories: Human | Large Structures | Kumar, P | Saenger, W | Uchanska-Ziegler, B | Vahedi-Faridi, A | Ziegler, A | Antibody | Disease mutation | Fab-hyb3 | Glycation | Glycoprotein | Hla | Hla-a010101 | Hla-a1 | Host-virus interaction | Human leukocyte antigen | Hyb3 | Immune response | Immune system | Immunoglobulin domain | Mage | Mage-a1 | Major histocompatibility complex | Melanoma associated antigen | Membrane | Mhc | Mhc i | Pyrrolidone carboxylic acid | Secreted | Sulfation | T-cell receptor | Tcr | Transmembrane | Tumor antigen
