2UWE

Large CDR3a loop alteration as a function of MHC mutation

Summary for 2UWE

• Entry DOI: 10.2210/pdb2uwe/pdb
• Related: 1A1M 1A1N 1A1O 1A6Z 1A9B 1A9E 1AGB 1AGC 1AGD 1AGE 1AGF 1AKJ 1AO7 1AQD 1B0G 1B0R 1BD2 1C16 1CE6 1CG9 1DE4 1DUY 1DUZ 1E27 1E28 1EEY 1EEZ 1EFX 1EXU 1GZP 1GZQ 1HHG 1HHH 1HHI 1HHJ 1HHK 1HLA 1HSA 1HSB 1I1F 1I1Y 1I4F 1I7R 1I7T 1I7U 1IM3 1IM9 1JF1 1JGD 1JGE 1JHT 1JNJ 1K5N 1KPR 1KTL 1LDS 1LP9 1M05 1M6O 1MHE 1MI5 1N2R 1OF2 1OGA 1OGT 1ONQ 1P7Q 1PY4 1Q94 1QEW 1QLF 1QQD 1QR1 1QRN 1QSE 1QSF 1QVO 1R3H 1S8D 1S9W 1S9X 1S9Y 1SYS 1SYV 1T1W 1T1X 1T1Y 1T1Z 1T20 1T21 1T22 1TMC 1TVB 1TVH 1UQS 1UR7 1UXS 1UXW 1VGK 1W0V 1W0W 1W72 1X7Q 1XH3 1XR8 1XR9 1XZ0 1YDP 1YPZ 1ZS8 1ZSD 1ZT4 2A83 2AK4 2AV1 2AV7 2AXF 2AXG 2BCK 2BNQ 2BNR 2BSR 2BSS 2BST 2BSU 2BSV 2BVQ 2C7U 2CII 2CIK 2CLR 2D31 2ESV 2F74 2F8O 2GJ6 2H26 2HJK 2HJL 2HLA 2JCC 3HLA
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, A-2 ALPHA CHAIN, BETA-2-MICROGLOBULIN, UNCHARACTERIZED PROTEIN C15ORF24, ... (6 entities in total)
• Functional Keywords: host-virus interaction, pyrrolidone carboxylic acid, glycoprotein, transmembrane, immune system, mhc i, membrane, receptor, class i mhc, hypothetical protein, immunoglobulin domain, immunoglobulin, immune response, tcr-pmhc complex, t cell signaling, disease mutation
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769; Membrane; Single-pass type I membrane protein (Potential): Q9NPA0
• Total number of polymer chains: 10
• Total formula weight: 186600.00

Authors

Miller, P.J.,Pazy, Y.,Conti, B.,Riddle, D.,Biddison, W.E.,Appella, E.,Collins, E.J. (deposition date: 2007-03-20, release date: 2007-09-25, Last modification date: 2023-12-13)

Primary citation

Miller, P.J.,Pazy, Y.,Conti, B.,Riddle, D.,Appella, E.,Collins, E.J.
Single Mhc Mutation Eliminates Enthalpy Associated with T Cell Receptor Binding.
J.Mol.Biol., 373:315-, 2007

PubMed Abstract: The keystone of the adaptive immune response is T cell receptor (TCR) recognition of peptide presented by major histocompatibility complex (pMHC) molecules. The crystal structure of AHIII TCR bound to MHC, HLA-A2, showed a large interface with an atypical binding orientation. MHC mutations in the interface of the proteins were tested for changes in TCR recognition. From the range of responses observed, three representative HLA-A2 mutants, T163A, W167A, and K66A, were selected for further study. Binding constants and co-crystal structures of the AHIII TCR and the three mutants were determined. K66 in HLA-A2 makes contacts with both peptide and TCR, and has been identified as a critical residue for recognition by numerous TCR. The K66A mutation resulted in the lowest AHIII T cell response and the lowest binding affinity, which suggests that the T cell response may correlate with affinity. Importantly, the K66A mutation does not affect the conformation of the peptide. The change in affinity appears to be due to a loss in hydrogen bonds in the interface as a result of a conformational change in the TCR complementarity-determining region 3 (CDR3) loop. Isothermal titration calorimetry confirmed the loss of hydrogen bonding by a large loss in enthalpy. Our findings are inconsistent with the notion that the CDR1 and CDR2 loops of the TCR are responsible for MHC restriction, while the CDR3 loops interact solely with the peptide. Instead, we present here an MHC mutation that does not change the conformation of the peptide, yet results in an altered conformation of a CDR3.

PubMed: 17825839
DOI: 10.1016/J.JMB.2007.07.028

Experimental method

X-RAY DIFFRACTION (2.4 Å)