PMID- 25028510 OWN - NLM STAT- MEDLINE DCOM- 20150122 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 35 DP - 2014 Aug 29 TI - Peptide-dependent conformational fluctuation determines the stability of the human leukocyte antigen class I complex. PG - 24680-90 LID - 10.1074/jbc.M114.566174 [doi] AB - In immune-mediated control of pathogens, human leukocyte antigen (HLA) class I presents various antigenic peptides to CD8(+) T-cells. Long-lived peptide presentation is important for efficient antigen-specific T-cell activation. Presentation time depends on the peptide sequence and the stability of the peptide-HLA complex (pHLA). However, the determinant of peptide-dependent pHLA stability remains elusive. Here, to reveal the pHLA stabilization mechanism, we examined the crystal structures of an HLA class I allomorph in complex with HIV-derived peptides and evaluated site-specific conformational fluctuations using NMR. Although the crystal structures of various pHLAs were almost identical independent of the peptides, fluctuation analyses identified a peptide-dependent minor state that would be more tightly packed toward the peptide. The minor population correlated well with the thermostability and cell surface presentation of pHLA, indicating that this newly identified minor state is important for stabilizing the pHLA and facilitating T-cell recognition. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Yanaka, Saeko AU - Yanaka S AD - From the Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 277-8562, Japan. FAU - Ueno, Takamasa AU - Ueno T AD - Center for AIDS Research, Kumamoto University, Kumamoto 860-0811, Japan, International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto 860-0811, Japan. FAU - Shi, Yi AU - Shi Y AD - Research Network of Immunity and Health, Beijing Institute of Life Science, Chinese Academy of Sciences, Beijing 100101, China, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Qi, Jianxun AU - Qi J AD - Research Network of Immunity and Health, Beijing Institute of Life Science, Chinese Academy of Sciences, Beijing 100101, China, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Gao, George F AU - Gao GF AD - Research Network of Immunity and Health, Beijing Institute of Life Science, Chinese Academy of Sciences, Beijing 100101, China, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China. FAU - Tsumoto, Kouhei AU - Tsumoto K AD - From the Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 277-8562, Japan, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo 108-8693, Japan, Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo 108-8693, Japan, and tsumoto@k.u-tokyo.ac.jp. FAU - Sugase, Kenji AU - Sugase K AD - Bioorganic Research Institute, Suntory Foundation for Life Sciences, Osaka 618-8503, Japan sugase@sunbor.or.jp. LA - eng SI - PDB/1A1N SI - PDB/1A9B SI - PDB/1A9E SI - PDB/1CG9 SI - PDB/1XH3 SI - PDB/1ZHK SI - PDB/1ZSD SI - PDB/2AXG SI - PDB/2CIK SI - PDB/2FYY SI - PDB/2H6P SI - PDB/2NX5 SI - PDB/3LKN SI - PDB/3LKO SI - PDB/3LKP SI - PDB/3LKQ SI - PDB/3LKR SI - PDB/3LKS SI - PDB/3MV7 SI - PDB/3MV8 SI - PDB/3MV9 SI - PDB/4LNR PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140715 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Peptides) SB - IM MH - Amino Acid Sequence MH - Crystallography, X-Ray MH - Histocompatibility Antigens Class I/*chemistry MH - Humans MH - Models, Molecular MH - Peptides/*chemistry MH - Protein Conformation PMC - PMC4148890 OTO - NOTNLM OT - Major Histocompatibility Complex (MHC) OT - Nuclear Magnetic Resonance (NMR) OT - Protein Dynamic OT - Protein Stability OT - Thermodynamics EDAT- 2014/07/17 06:00 MHDA- 2015/01/23 06:00 PMCR- 2015/08/29 CRDT- 2014/07/17 06:00 PHST- 2014/07/17 06:00 [entrez] PHST- 2014/07/17 06:00 [pubmed] PHST- 2015/01/23 06:00 [medline] PHST- 2015/08/29 00:00 [pmc-release] AID - S0021-9258(20)31998-0 [pii] AID - M114.566174 [pii] AID - 10.1074/jbc.M114.566174 [doi] PST - ppublish SO - J Biol Chem. 2014 Aug 29;289(35):24680-90. doi: 10.1074/jbc.M114.566174. Epub 2014 Jul 15.