2fwo
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MHC Class I H-2Kd heavy chain in complex with beta-2microglobulin and peptide derived from influenza nucleoprotein
OverviewOverview
Classic major histocompatibility complex (MHC) proteins associate with, antigen- and self-derived peptides in an allele-specific manner. Herein we, present the crystal structure of the MHC class I protein H-2K(d) (K(d)), expressed by BALB/c mice in complex with an antigenic peptide derived from, influenza A/PR/8/34 nucleoprotein (Flu, residues 147-155, TYQRTRALV)., Analysis of our structure in conjunction with the sequences of naturally, processed epitopes provides a comprehensive understanding of the dominant, K(d) peptide-binding motif. We find that Flu residues Tyr(P2), Thr(P5), and Val(P9) are sequestered into the B, C, and F pockets of the K(d), groove, respectively. The shape and chemistry of the polymorphic B pocket, make it an optimal binding site for the side chain of Tyr(P2) as the, dominant anchoring residue of nonameric peptides. The non-polar F pocket, limits the amino acid repertoire at P9 to hydrophobic residues such as, Ile, Leu, or Val, whereas the C pocket restricts the size of the, P5-anchoring side chain. We also show that Flu is accommodated in the, complex through an unfavorable kink in the otherwise extended peptide, backbone due to the presence of a prominent ridge in the K(d) groove., Surprisingly, this backbone conformation is strikingly similar to, D(b)-presented peptides despite the fact that these proteins employ, distinct motif-anchoring strategies. The results presented in this study, provide a solid foundation for the understanding of K(d)-restricted, antigen presentation and recognition events.
About this StructureAbout this Structure
2FWO is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Structural definition of the H-2Kd peptide-binding motif., Mitaksov V, Fremont DH, J Biol Chem. 2006 Apr 14;281(15):10618-25. Epub 2006 Feb 10. PMID:16473882
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