6IEX

Crystal structure of HLA-B*4001 in complex with SARS-CoV derived peptide N216-225 GETALALLLL

Summary for 6IEX

• Entry DOI: 10.2210/pdb6iex/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, GLY-GLU-THR-ALA-LEU-ALA-LEU-LEU-LEU-LEU, ... (4 entities in total)
• Functional Keywords: hla-b*4001, sars-cov, n216-225, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 44686.74

Authors

Ji, W.,Niu, L.,Peng, W.,Zhang, Y.,Shi, Y.,Qi, J.,Gao, G.F.,Liu, W.J. (deposition date: 2018-09-17, release date: 2019-09-18, Last modification date: 2024-10-16)

Primary citation

Ji, W.,Niu, L.,Peng, W.,Zhang, Y.,Cheng, H.,Gao, F.,Shi, Y.,Qi, J.,Gao, G.F.,Liu, W.J.
Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner.
Mol.Immunol., 112:274-282, 2019

PubMed Abstract: The viral peptides presentation by major histocompatibility complex class I (MHC I) molecules play a pivotal role in T-cell recognition and the subsequent virus clearance. This process is delicately adjusted by the variant residues of MHC I, especially the residues in the peptide binding groove (PBG). In a series of MHC I molecules, a salt bridge is formed above the N-terminus of the peptides. However, the potential impact of the salt bridge on peptide binding and T-cell receptor (TCR) recognition of MHC I, as well as the corresponding molecular basis, are still largely unknown. Herein, we determined the structures of HLA-B*4001 and H-2K in which two different types of salt bridges (Arg62-Glu163 or Arg66-Glu163) across the PBG were observed. Although the two salt bridges led to different conformation shifts of both the MHC I α helix and the peptides, binding of the peptides with the salt bridge residues was relatively conserved. Furthermore, through a series of in vitro and in vivo investigations, we found that MHC I mutations that disrupt the salt bridge alleviate peptide binding and can weaken the TCR recognition of MHC I-peptide complexes. Our study may provide key references for understanding MHC I-restricted peptide recognition by T-cells.

PubMed: 31226552
DOI: 10.1016/j.molimm.2019.06.005

Experimental method

X-RAY DIFFRACTION (2.314 Å)