|
|
| Line 1: |
Line 1: |
| | | | |
| | ==H-2Db complex with human gp100== | | ==H-2Db complex with human gp100== |
| - | <StructureSection load='3cc5' size='340' side='right' caption='[[3cc5]], [[Resolution|resolution]] 1.91Å' scene=''> | + | <StructureSection load='3cc5' size='340' side='right'caption='[[3cc5]], [[Resolution|resolution]] 1.91Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3cc5]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CC5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3CC5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3cc5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CC5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CC5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H2-D1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H2-D1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3cc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cc5 OCA], [http://pdbe.org/3cc5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3cc5 RCSB], [http://www.ebi.ac.uk/pdbsum/3cc5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3cc5 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cc5 OCA], [https://pdbe.org/3cc5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cc5 RCSB], [https://www.ebi.ac.uk/pdbsum/3cc5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cc5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/PMEL_HUMAN PMEL_HUMAN]] Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.<ref>PMID:11694580</ref> [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [[https://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[https://www.uniprot.org/uniprot/PMEL_HUMAN PMEL_HUMAN]] Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.<ref>PMID:11694580</ref> [[https://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 31: |
Line 31: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| - | *[[Major histocompatibility complex|Major histocompatibility complex]] | + | *[[MHC 3D structures|MHC 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Achour, A]] | | [[Category: Achour, A]] |
| Structural highlights
Function
[HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. [PMEL_HUMAN] Plays a central role in the biogenesis of melanosomes. Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity.[1] [B2MG_MOUSE] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Immunogenicity of tumor-associated antigens (TAA) is often weak because many TAA are autoantigens for which the T-cell repertoire is sculpted by tolerance mechanisms. Substitutions at main anchor positions to increase the complementarity between the peptide and the MHC class I (MHC-I) binding cleft constitute a common procedure to improve binding capacity and immunogenicity of TAA. However, such alterations are tailored for each MHC-I allele and may recruit different CTL specificities through conformational changes in the targeted peptides. Comparative analysis of substituted melanoma-differentiation antigen gp100 in complex with H-2D(b) revealed that combined introduction of glycine and proline residues at the nonanchor positions 2 and 3, respectively, resulted in an agonistic altered peptide with dramatically enhanced binding affinity, stability, and immunogenicity of this TAA. Peptide vaccination using the p2Gp3P-altered peptide version of gp100 induced high frequencies of melanoma-specific CTL in the endogenous CD8+ repertoire. Crystal structure analysis of MHC/peptide complexes revealed that the conformation of the modified p2Gp3P-peptide was similar to the wild-type peptide, and indicated that this mimotope was stabilized through interactions between peptide residue p3P and the tyrosine residue Y159 that is conserved among most known MHC-I molecules throughout mammalian species. Our results may provide an alternative approach to enhance MHC stabilization capacity and immunogenicity of low-affinity peptides for induction of robust tumor-specific CTL.
Design of agonistic altered peptides for the robust induction of CTL directed towards H-2Db in complex with the melanoma-associated epitope gp100.,van Stipdonk MJ, Badia-Martinez D, Sluijter M, Offringa R, van Hall T, Achour A Cancer Res. 2009 Oct 1;69(19):7784-92. Epub 2009 Sep 29. PMID:19789338[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Berson JF, Harper DC, Tenza D, Raposo G, Marks MS. Pmel17 initiates premelanosome morphogenesis within multivesicular bodies. Mol Biol Cell. 2001 Nov;12(11):3451-64. PMID:11694580
- ↑ van Stipdonk MJ, Badia-Martinez D, Sluijter M, Offringa R, van Hall T, Achour A. Design of agonistic altered peptides for the robust induction of CTL directed towards H-2Db in complex with the melanoma-associated epitope gp100. Cancer Res. 2009 Oct 1;69(19):7784-92. Epub 2009 Sep 29. PMID:19789338 doi:10.1158/0008-5472.CAN-09-1724
|
