3L3H

X-ray crystal structure of the F6A mutant of influenza A acid polymerase epitope PA224 bound to murine H2-Db MHC

Summary for 3L3H

• Entry DOI: 10.2210/pdb3l3h/pdb
• Related: 1YN6 1YN7 3L3D 3L3G 3L3I 3L3J 3L3K
• Descriptor: H-2 class I histocompatibility antigen, D-B alpha chain, Beta-2-microglobulin, 10-mer peptide from Polymerase acidic protein, ... (4 entities in total)
• Functional Keywords: animals antigens, viral epitopes, t-lymphocyte histocompatibility antigens, mice antigen, t-cell, t-lymphocytes, glycoprotein, immune response, membrane, mhc i, transmembrane, immunoglobulin domain, secreted, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01899; Secreted: P01887
• Total number of polymer chains: 3
• Total formula weight: 44845.21

Authors

Welland, A.,Clements, C.S.,Dunstone, M.A.,Rossjohn, J. (deposition date: 2009-12-17, release date: 2010-03-16, Last modification date: 2024-10-30)

Primary citation

Theodossis, A.,Guillonneau, C.,Welland, A.,Ely, L.K.,Clements, C.S.,Williamson, N.A.,Webb, A.I.,Wilce, J.A.,Mulder, R.J.,Dunstone, M.A.,Doherty, P.C.,McCluskey, J.,Purcell, A.W.,Turner, S.J.,Rossjohn, J.
Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition
Proc.Natl.Acad.Sci.USA, 107:5534-5539, 2010

PubMed Abstract: Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered to function as a series of "independent pegs" that either anchor the peptide (p) to the MHC-I and/or interact with the spectrum of alphabeta-T-cell receptors (TCRs) specific for the pMHC-I epitope in question. Mining of the extensive pMHC-I structural database established that many self- and viral peptides show extensive and direct interresidue interactions, an unexpected finding that has led us to the idea of "constrained" peptides. Mutational analysis of two constrained peptides (the HLA B44 restricted self-peptide (B44DPalpha-EEFGRAFSF) and an H2-D(b) restricted influenza peptide (D(b)PA, SSLENFRAYV) demonstrated that the conformation of the prominently exposed arginine in both peptides was governed by interactions with MHC-I-orientated flanking residues from the peptide itself. Using reverse genetics in a murine influenza model, we revealed that mutation of an MHC-I-orientated residue (SSLENFRAYV --> SSLENARAYV) within the constrained PA peptide resulted in a diminished cytotoxic T lymphocyte (CTL) response and the recruitment of a limited pMHC-I specific TCR repertoire. Interactions between individual peptide positions can thus impose fine control on the conformation of pMHC-I epitopes, whereas the perturbation of such constraints can lead to a previously unappreciated mechanism of viral escape.

PubMed: 20212169
DOI: 10.1073/pnas.1000032107

Experimental method

X-RAY DIFFRACTION (2.7 Å)