1zhb
From Proteopedia
(New page: 200px<br /><applet load="1zhb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zhb, resolution 2.70Å" /> '''Crystal Structure Of...) |
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| - | [[Image:1zhb.gif|left|200px]]<br /><applet load="1zhb" size=" | + | [[Image:1zhb.gif|left|200px]]<br /><applet load="1zhb" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1zhb, resolution 2.70Å" /> | caption="1zhb, resolution 2.70Å" /> | ||
'''Crystal Structure Of The Murine Class I Major Histocompatibility Complex Of H-2Db, B2-Microglobulin, and a 9-Residue Peptide Derived from rat dopamine beta-monooxigenase'''<br /> | '''Crystal Structure Of The Murine Class I Major Histocompatibility Complex Of H-2Db, B2-Microglobulin, and a 9-Residue Peptide Derived from rat dopamine beta-monooxigenase'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Molecular mimicry of self-epitopes by viral antigens is one possible | + | Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (KAVYNFATC/M), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM, has also been identified. We herein report the crystal structure of H-2Db.rDBM and a comparison with the crystal structures of the cross-reactive H-2Db.gp33 and non-cross-reactive H-2Db.gp33 (V3L) escape variant (KALYNFATM, 88% identity to gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented in nearly identical manners by H-2Db, with a striking juxtaposition of the central sections of both peptides from residues p3 to p7. The structural similarity provides H-2Db in complex with either a virus-derived or a dopamine beta-mono-oxygenase-derived peptide with a shared antigenic identity that conserves the positioning of the heavy chain and peptide residues that interact with the T cell receptor (TCR). This stands in contrast to the structure of H-2Db.gp33 (V3L), in which a single conserved mutation, also present in rDBM, induces large movements of both the peptide backbone and the side chains that interact with the TCR. The TCR-interacting surfaces of the H-2Db.rDBM and H-2Db.gp33 major histocompatibility complexes are very similar with regard to shape, topology, and charge distribution, providing a structural basis for CD8 T cell activation by molecular mimicry and potential subsequent development of autoreactivity. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZHB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Dopamine_beta-monooxygenase Dopamine beta-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.17.1 1.14.17.1] Full crystallographic information is available from [http:// | + | 1ZHB is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Dopamine_beta-monooxygenase Dopamine beta-monooxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.17.1 1.14.17.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZHB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Achour, A.]] | [[Category: Achour, A.]] | ||
| - | [[Category: Harris, R | + | [[Category: Harris, R A.]] |
[[Category: Karre, K.]] | [[Category: Karre, K.]] | ||
[[Category: Michaelsson, J.]] | [[Category: Michaelsson, J.]] | ||
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[[Category: tcr-crossreactivity]] | [[Category: tcr-crossreactivity]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:15:37 2008'' |
Revision as of 14:15, 21 February 2008
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Crystal Structure Of The Murine Class I Major Histocompatibility Complex Of H-2Db, B2-Microglobulin, and a 9-Residue Peptide Derived from rat dopamine beta-monooxigenase
Overview
Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (KAVYNFATC/M), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM, has also been identified. We herein report the crystal structure of H-2Db.rDBM and a comparison with the crystal structures of the cross-reactive H-2Db.gp33 and non-cross-reactive H-2Db.gp33 (V3L) escape variant (KALYNFATM, 88% identity to gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented in nearly identical manners by H-2Db, with a striking juxtaposition of the central sections of both peptides from residues p3 to p7. The structural similarity provides H-2Db in complex with either a virus-derived or a dopamine beta-mono-oxygenase-derived peptide with a shared antigenic identity that conserves the positioning of the heavy chain and peptide residues that interact with the T cell receptor (TCR). This stands in contrast to the structure of H-2Db.gp33 (V3L), in which a single conserved mutation, also present in rDBM, induces large movements of both the peptide backbone and the side chains that interact with the TCR. The TCR-interacting surfaces of the H-2Db.rDBM and H-2Db.gp33 major histocompatibility complexes are very similar with regard to shape, topology, and charge distribution, providing a structural basis for CD8 T cell activation by molecular mimicry and potential subsequent development of autoreactivity.
About this Structure
1ZHB is a Protein complex structure of sequences from Mus musculus. Active as Dopamine beta-monooxygenase, with EC number 1.14.17.1 Full crystallographic information is available from OCA.
Reference
A structural basis for CD8+ T cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity., Sandalova T, Michaelsson J, Harris RA, Odeberg J, Schneider G, Karre K, Achour A, J Biol Chem. 2005 Jul 22;280(29):27069-75. Epub 2005 Apr 21. PMID:15845547
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