2FWO

MHC Class I H-2Kd heavy chain in complex with beta-2microglobulin and peptide derived from influenza nucleoprotein

Summary for 2FWO

• Entry DOI: 10.2210/pdb2fwo/pdb
• Descriptor: H-2 class I histocompatibility antigen, K-D alpha chain, Beta-2-microglobulin, TYQRTRALV peptide from Nucleoprotein, ... (4 entities in total)
• Functional Keywords: mhc, antigens/peptides/epitopes, antigen processing/presentation, immune system-viral protein complex, immune system/viral protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01902; Secreted: P01887
• Total number of polymer chains: 3
• Total formula weight: 45855.40

Authors

Mitaksov, V.,Fremont, D.H. (deposition date: 2006-02-02, release date: 2006-02-21, Last modification date: 2023-08-30)

Primary citation

Mitaksov, V.,Fremont, D.H.
Structural Definition of the H-2Kd Peptide-binding Motif.
J.Biol.Chem., 281:10618-10625, 2006

PubMed Abstract: 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.

PubMed: 16473882
DOI: 10.1074/jbc.M510511200

Experimental method

X-RAY DIFFRACTION (2.6 Å)