3unh: Difference between revisions
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==Mouse 20S immunoproteasome== | |||
<StructureSection load='3unh' size='340' side='right'caption='[[3unh]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3unh]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UNH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UNH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></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=3unh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3unh OCA], [https://pdbe.org/3unh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3unh RCSB], [https://www.ebi.ac.uk/pdbsum/3unh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3unh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PSA2_MOUSE PSA2_MOUSE] The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 A resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit beta5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of beta5c/X but not beta5i, thereby explaining the selectivity of PR-957 for beta5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders. | |||
Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity.,Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M Cell. 2012 Feb 17;148(4):727-38. PMID:22341445<ref>PMID:22341445</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3unh" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Proteasome|Proteasome]] | *[[Proteasome 3D structures|Proteasome 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Basler M]] | |||
[[Category: Basler | [[Category: Groettrup M]] | ||
[[Category: Groettrup | [[Category: Groll M]] | ||
[[Category: Groll | [[Category: Heinemeyer W]] | ||
[[Category: Heinemeyer | [[Category: Huber E]] | ||
[[Category: Huber | [[Category: Kirk C]] | ||
[[Category: Kirk | [[Category: Schwab R]] | ||
[[Category: Schwab | |||
Latest revision as of 05:31, 21 November 2024
Mouse 20S immunoproteasomeMouse 20S immunoproteasome
Structural highlights
FunctionPSA2_MOUSE The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation. Publication Abstract from PubMedConstitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 A resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit beta5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of beta5c/X but not beta5i, thereby explaining the selectivity of PR-957 for beta5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity.,Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M Cell. 2012 Feb 17;148(4):727-38. PMID:22341445[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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