1vad
From Proteopedia
(New page: 200px<br /><applet load="1vad" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vad, resolution 2.5Å" /> '''MHC CLASS I H-2KB HEA...) |
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| - | [[Image:1vad.gif|left|200px]]<br /><applet load="1vad" size=" | + | [[Image:1vad.gif|left|200px]]<br /><applet load="1vad" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1vad, resolution 2.5Å" /> | caption="1vad, resolution 2.5Å" /> | ||
'''MHC CLASS I H-2KB HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND YEAST ALPHA-GLUCOSIDASE'''<br /> | '''MHC CLASS I H-2KB HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND YEAST ALPHA-GLUCOSIDASE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Sequence analysis of peptides naturally presented by major | + | Sequence analysis of peptides naturally presented by major histocompatibility complex (MHC) class I molecules has revealed allele-specific motifs in which the peptide length and the residues observed at certain positions are restricted. Nevertheless, peptides containing the standard motif often fail to bind with high affinity or form physiologically stable complexes. Here we present the crystal structure of a well-characterized antigenic peptide from ovalbumin [OVA-8, ovalbumin-(257-264), SIINFEKL] in complex with the murine MHC class I H-2Kb molecule at 2.5-A resolution. Hydrophobic peptide residues Ile-P2 and Phe-P5 are packed closely together into binding pockets B and C, suggesting that the interplay of peptide anchor (P5) and secondary anchor (P2) residues can couple the preferred sequences at these positions. Comparison with the crystal structures of H-2Kb in complex with peptides VSV-8 (RGYVYQGL) and SEV-9 (FAPGNYPAL), where a Tyr residue is used as the C pocket anchor, reveals that the conserved water molecule that binds into the B pocket and mediates hydrogen bonding from the buried anchor hydroxyl group could not be likewise positioned if the P2 side chain were of significant size. Based on this structural evidence, H-2Kb has at least two submotifs: one with Tyr at P5 (or P6 for nonamer peptides) and a small residue at P2 (i.e., Ala or Gly) and another with Phe at P5 and a medium-sized hydrophobic residue at P2 (i.e., Ile). Deciphering of these secondary submotifs from both crystallographic and immunological studies of MHC peptide binding should increase the accuracy of T-cell epitope prediction. |
==About this Structure== | ==About this Structure== | ||
| - | 1VAD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/Alpha-glucosidase Alpha-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.20 3.2.1.20] Full crystallographic information is available from [http:// | + | 1VAD is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Active as [http://en.wikipedia.org/wiki/Alpha-glucosidase Alpha-glucosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.20 3.2.1.20] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VAD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Saccharomyces cerevisiae]] | [[Category: Saccharomyces cerevisiae]] | ||
| - | [[Category: Fremont, D | + | [[Category: Fremont, D H.]] |
| - | [[Category: Wilson, I | + | [[Category: Wilson, I A.]] |
[[Category: class i major histocompatibility complex]] | [[Category: class i major histocompatibility complex]] | ||
[[Category: histocompatibility antigen]] | [[Category: histocompatibility antigen]] | ||
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[[Category: peptide]] | [[Category: peptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:33:10 2008'' |
Revision as of 13:33, 21 February 2008
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MHC CLASS I H-2KB HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND YEAST ALPHA-GLUCOSIDASE
Overview
Sequence analysis of peptides naturally presented by major histocompatibility complex (MHC) class I molecules has revealed allele-specific motifs in which the peptide length and the residues observed at certain positions are restricted. Nevertheless, peptides containing the standard motif often fail to bind with high affinity or form physiologically stable complexes. Here we present the crystal structure of a well-characterized antigenic peptide from ovalbumin [OVA-8, ovalbumin-(257-264), SIINFEKL] in complex with the murine MHC class I H-2Kb molecule at 2.5-A resolution. Hydrophobic peptide residues Ile-P2 and Phe-P5 are packed closely together into binding pockets B and C, suggesting that the interplay of peptide anchor (P5) and secondary anchor (P2) residues can couple the preferred sequences at these positions. Comparison with the crystal structures of H-2Kb in complex with peptides VSV-8 (RGYVYQGL) and SEV-9 (FAPGNYPAL), where a Tyr residue is used as the C pocket anchor, reveals that the conserved water molecule that binds into the B pocket and mediates hydrogen bonding from the buried anchor hydroxyl group could not be likewise positioned if the P2 side chain were of significant size. Based on this structural evidence, H-2Kb has at least two submotifs: one with Tyr at P5 (or P6 for nonamer peptides) and a small residue at P2 (i.e., Ala or Gly) and another with Phe at P5 and a medium-sized hydrophobic residue at P2 (i.e., Ile). Deciphering of these secondary submotifs from both crystallographic and immunological studies of MHC peptide binding should increase the accuracy of T-cell epitope prediction.
About this Structure
1VAD is a Protein complex structure of sequences from Mus musculus and Saccharomyces cerevisiae. Active as Alpha-glucosidase, with EC number 3.2.1.20 Full crystallographic information is available from OCA.
Reference
Crystal structure of an H-2Kb-ovalbumin peptide complex reveals the interplay of primary and secondary anchor positions in the major histocompatibility complex binding groove., Fremont DH, Stura EA, Matsumura M, Peterson PA, Wilson IA, Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2479-83. PMID:7708669
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