3KWW

Crystal structure of the 'restriction triad' mutant of HLA B*3508, beta-2-microglobulin and EBV peptide

Summary for 3KWW

• Entry DOI: 10.2210/pdb3kww/pdb
• Related: 3KXF
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, peptide from Trans-activator protein BZLF1, ... (7 entities in total)
• Functional Keywords: mhc-peptide, hla, disulfide bond, immune response, membrane, mhc i, polymorphism, immunoglobulin domain, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30685; Secreted . Note=(Microbial infection) In the presence of M: P61769; Host nucleus : P03206
• Total number of polymer chains: 3
• Total formula weight: 46376.34

Authors

Archbold, J.K.,Tynan, F.E.,Gras, S.,Rossjohn, J. (deposition date: 2009-12-01, release date: 2010-06-09, Last modification date: 2024-10-30)

Primary citation

Burrows, S.R.,Chen, Z.,Archbold, J.K.,Tynan, F.E.,Beddoe, T.,Kjer-Nielsen, L.,Miles, J.J.,Khanna, R.,Moss, D.J.,Liu, Y.C.,Gras, S.,Kostenko, L.,Brennan, R.M.,Clements, C.S.,Brooks, A.G.,Purcell, A.W.,McCluskey, J.,Rossjohn, J.
Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability
Proc.Natl.Acad.Sci.USA, 2010

PubMed Abstract: alphabeta T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.

PubMed: 20483993
DOI: 10.1073/pnas.1004926107

Experimental method

X-RAY DIFFRACTION (2.18 Å)