2fwo
From Proteopedia
(New page: 200px<br /><applet load="2fwo" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fwo, resolution 2.60Å" /> '''MHC Class I H-2Kd he...) |
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| - | [[Image:2fwo.gif|left|200px]]<br /><applet load="2fwo" size=" | + | [[Image:2fwo.gif|left|200px]]<br /><applet load="2fwo" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2fwo, resolution 2.60Å" /> | caption="2fwo, resolution 2.60Å" /> | ||
'''MHC Class I H-2Kd heavy chain in complex with beta-2microglobulin and peptide derived from influenza nucleoprotein'''<br /> | '''MHC Class I H-2Kd heavy chain in complex with beta-2microglobulin and peptide derived from influenza nucleoprotein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Classic major histocompatibility complex (MHC) proteins associate with | + | 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 Structure== | ==About this Structure== | ||
| - | 2FWO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 2FWO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FWO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Fremont, D | + | [[Category: Fremont, D H.]] |
[[Category: Mitaksov, V.]] | [[Category: Mitaksov, V.]] | ||
[[Category: antigen processing/presentation]] | [[Category: antigen processing/presentation]] | ||
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[[Category: mhc]] | [[Category: mhc]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:25:57 2008'' |
Revision as of 15:26, 21 February 2008
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MHC Class I H-2Kd heavy chain in complex with beta-2microglobulin and peptide derived from influenza nucleoprotein
Overview
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 Structure
2FWO is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
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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