2X4P

Crystal structure of MHC CLass I HLA-A2.1 bound to a photocleavable peptide

Summary for 2X4P

• Entry DOI: 10.2210/pdb2x4p/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 1OF2 1OGA 1OGT 1ONQ 1P7Q 1PY4 1Q94 1QEW 1QLF 1QQD 1QR1 1QRN 1QSE 1QSF 1QVO 1R3H 1S9W 1S9X 1S9Y 1SYS 1SYV 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 2BVO 2BVP 2BVQ 2C7U 2CII 2CIK 2CLR 2D31 2ESV 2F74 2F8O 2GJ6 2H26 2HJK 2HJL 2HLA 2J8U 2JCC 2UWE 2V2W 2V2X 2VB5 2VLJ 2VLK 2VLL 2VLR 2X4N 2X4O 2X4Q 2X4R 2X4S 2X4T 2X4U 3HLA
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, A-2.1, BETA-2-MICROGLOBULIN, HLA-A2.1-RESTRICTED INFLUENZA A MATRIX EPITOPE, ... (6 entities in total)
• Functional Keywords: glycoprotein, immune system, immunoglobulin domain, matrix (m1)
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 6
• Total formula weight: 91386.32

Authors

Celie, P.H.N.,Toebes, M.,Rodenko, B.,Ovaa, H.,Perrakis, A.,Schumacher, T.N.M. (deposition date: 2010-02-02, release date: 2010-03-02, Last modification date: 2023-12-20)

Primary citation

Rodenko, B.,Toebes, M.,Celie, P.H.N.,Perrakis, A.,Schumacher, T.N.M.,Ovaa, H.
Class I Major Histocompatibility Complexes Loaded by a Periodate Trigger.
J.Am.Chem.Soc., 131:12305-, 2009

PubMed Abstract: Class I major histocompatibility complexes (MHCs) present peptide ligands on the cell surface for recognition by appropriate cytotoxic T cells. The unstable nature of unliganded MHC necessitates the production of recombinant class I complexes through in vitro refolding reactions in the presence of an added excess of peptides. This strategy is not amenable to high-throughput production of vast collections of class I complexes. To address this issue, we recently designed photocaged MHC ligands that can be cleaved by a UV light trigger in the MHC bound state under conditions that do not affect the integrity of the MHC structure. The results obtained with photocaged MHC ligands demonstrate that conditional MHC ligands can form a generally applicable concept for the creation of defined peptide-MHCs. However, the use of UV exposure to mediate ligand exchange is unsuited for a number of applications, due to the lack of UV penetration through cell culture systems and due to the transfer of heat upon UV irradiation, which can induce evaporation. To overcome these limitations, here, we provide proof-of-concept for the generation of defined peptide-MHCs by chemical trigger-induced ligand exchange. The crystal structure of the MHC with the novel chemosensitive ligand showcases that the ligand occupies the expected binding site, in a conformation where the hydroxyl groups should be reactive to periodate. We proceed to validate this technology by producing peptide-MHCs that can be used for T cell detection. The methodology that we describe here should allow loading of MHCs with defined peptides in cell culture devices, thereby permitting antigen-specific T cell expansion and purification for cell therapy. In addition, this technology will be useful to develop miniaturized assay systems for performing high-throughput screens for natural and unnatural MHC ligands.

PubMed: 19655751
DOI: 10.1021/JA9037565

Experimental method

X-RAY DIFFRACTION (2.3 Å)