5XMF

Crystal structure of feline MHC class I for 2,1 angstrom

Summary for 5XMF

• Entry DOI: 10.2210/pdb5xmf/pdb
• Descriptor: MHC class I antigen alpha chain, Beta-2-microglobulin, Gag polyprotein, ... (4 entities in total)
• Functional Keywords: domestic cats, mhc i, feline immunodeficiency virus, ctl immunity, immune system
• Biological source: Felis catus (Cat); More
• Total number of polymer chains: 3
• Total formula weight: 44558.46

Authors

Liang, R.,Sun, Y.,Wang, J.,Wu, Y.,Zhang, N.,Xia, C. (deposition date: 2017-05-15, release date: 2017-12-13, Last modification date: 2024-10-16)

Primary citation

Liang, R.,Sun, Y.,Liu, Y.,Wang, J.,Wu, Y.,Li, Z.,Ma, L.,Zhang, N.,Zhang, L.,Wei, X.,Qu, Z.,Zhang, N.,Xia, C.
Major Histocompatibility Complex Class I (FLA-E*01801) Molecular Structure in Domestic Cats Demonstrates Species-Specific Characteristics in Presenting Viral Antigen Peptides
J. Virol., 92:-, 2018

PubMed Abstract: Feline immunodeficiency virus (FIV) infection in domestic cats is the smallest usable natural model for lentiviral infection studies. FLA-E*01801 was applied to FIV AIDS vaccine research. We determined the crystal structure of FLA-E*01801 complexed with a peptide derived from FIV (gag positions 40 to 48; RMANVSTGR [RMA9]). The A pocket of the FLA-E*01801 complex plays a valuable restrictive role in peptide binding. Mutation experiments and circular-dichroism (CD) spectroscopy revealed that peptides with Asp at the first position (P1) could not bind to FLA-E*01801. The crystal structure and refolding of the mutant FLA-E*01801 complex demonstrated that Glu and Trp in the A pocket play important roles in restricting P1D. The B pocket of the FLA-E*01801 complex accommodates M/T/A/V/I/L/S residues, whereas the negatively charged F pocket prefers R/K residues. Based on the peptide binding motif, 125 FLA-E*01801-restricted FIV nonapeptides (San Diego isolate) were identified. Our results provide the structural basis for peptide presentation by the FLA-E*01801 molecule, especially A pocket restriction on peptide binding, and identify the potential cytotoxic T lymphocyte (CTL) epitope peptides of FIV presented by FLA-E*01801. These results will benefit both the reasonable design of FLA-E*01801-restricted CTL epitopes and the further development of the AIDS vaccine. Feline immunodeficiency virus (FIV) is a viral pathogen in cats, and this infection is the smallest usable natural model for lentivirus infection studies. To examine how FLA I presents FIV epitope peptides, we crystallized and solved the first classic feline major histocompatibility complex class I (MHC-I) molecular structure. Surprisingly, pocket A restricts peptide binding. Trp blocks the left side of pocket A, causing P1D to conflict with Glu We also identified the FLA-E*01801 binding motif X (except D)-(M/T/A/V/I/L/S)-X-X-X-X-X-X-(R/K) based on structural and biochemical experiments. We identified 125 FLA-E*01801-restricted nonapeptides from FIV. These results are valuable for developing peptide-based FIV and human immunodeficiency virus (HIV) vaccines and for studying how MHC-I molecules present peptides.

PubMed: 29263258
DOI: 10.1128/JVI.01631-17

Experimental method

X-RAY DIFFRACTION (2.1 Å)