8f6a: Difference between revisions

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-'''Unreleased structure'''
-The entry 8f6a is ON HOLD
+==Thermoplasma acidophilum 20S proteasome - wild type==
+<StructureSection load='8f6a' size='340' side='right'caption='[[8f6a]], [[Resolution|resolution]] 2.06&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8f6a]] is a 28 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermoplasma_acidophilum Thermoplasma acidophilum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8F6A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8F6A FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.06&#8491;</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=8f6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8f6a OCA], [https://pdbe.org/8f6a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8f6a RCSB], [https://www.ebi.ac.uk/pdbsum/8f6a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8f6a ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/PSB_THEAC PSB_THEAC] Component of the proteasome core, a large protease complex with broad specificity involved in protein degradation. The T.acidophilum proteasome is able to cleave oligopeptides after Tyr, Leu, Phe, and to a lesser extent after Glu and Arg. Thus, displays chymotrypsin-like activity and low level of caspase-like and trypsin-like activities.<ref>PMID:8999862</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Considering the link between neurodegenerative diseases and impaired proteasome function, and the neuro-protective impact of enhanced proteasome activity in animal models, it's crucial to understand proteasome activation mechanisms. A hydrophobic-tyrosine-any residue (HbYX) motif on the C-termini of proteasome-activating complexes independently triggers gate-opening of the 20S core particle for protein degradation; however, the causal allosteric mechanism remains unclear. Our study employs a structurally irreducible dipeptide HbYX mimetic to investigate the allosteric mechanism of gate-opening in the archaeal proteasome. High-resolution cryo-EM structures pinpoint vital residues and conformational changes in the proteasome alpha-subunit implicated in HbYX-dependent activation. Using point mutations, we simulated the HbYX-bound state, providing support for our mechanistic model. We discerned four main mechanistic elements triggering gate-opening: 1) back-loop rearrangement adjacent to K66, 2) intra- and inter- alpha subunit conformational changes, 3) occupancy of the hydrophobic pocket, and 4) a highly conserved isoleucine-threonine pair in the 20S channel stabilizing the open and closed states, termed the "IT switch." Comparison of different complexes unveiled convergent and divergent mechanism of 20S gate-opening among HbYX-dependent and independent activators. This study delivers a detailed molecular model for HbYX-dependent 20S gate-opening, enabling the development of small molecule proteasome activators that hold promise to treat neurodegenerative diseases.
-Authors:
+High resolution structures define divergent and convergent mechanisms of archaeal proteasome activation.,Chuah JJY, Rexroad MS, Smith DM Commun Biol. 2023 Jul 15;6(1):733. doi: 10.1038/s42003-023-05123-3. PMID:37454196<ref>PMID:37454196</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8f6a" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Thermoplasma acidophilum]]
+[[Category: Chuah J]]
+[[Category: Smith D]]