6kwx
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==cryo-EM structure of human PA200== | |
| + | <StructureSection load='6kwx' size='340' side='right'caption='[[6kwx]], [[Resolution|resolution]] 3.75Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6kwx]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KWX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KWX FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=I6P:INOSITOL+1,2,3,4,5,6-HEXAKISPHOSPHATE'>I6P</scene>, <scene name='pdbligand=K0W:[(1~{S},2~{R},3~{R},4~{S},5~{S},6~{R})-2-[oxidanyl(phosphonooxy)phosphoryl]oxy-3,4,5,6-tetraphosphonooxy-cyclohexyl]+phosphono+hydrogen+phosphate'>K0W</scene></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=6kwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kwx OCA], [http://pdbe.org/6kwx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kwx RCSB], [http://www.ebi.ac.uk/pdbsum/6kwx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kwx ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PSME4_HUMAN PSME4_HUMAN]] Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its C-terminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.<ref>PMID:12093752</ref> <ref>PMID:18845680</ref> <ref>PMID:22550082</ref> <ref>PMID:23706739</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Proteasomes are highly abundant and conserved protease complexes that eliminate unwanted proteins in the cells. As a single-chain ATP-independent nuclear proteasome activator, proteasome activator 200 (PA200) associates with 20S core particle to form proteasome complex that catalyzes polyubiquitin-independent degradation of acetylated histones, thus playing a pivotal role in DNA repair and spermatogenesis. Here, we present cryo-electron microscopy (cryo-EM) structures of the human PA200-20S complex and PA200 at 2.72 A and 3.75 A, respectively. PA200 exhibits a dome-like architecture that caps 20S and uses its C-terminal YYA (Tyr-Tyr-Ala) to induce the alpha-ring rearrangements and partial opening of the 20S gate. Our structural data also indicate that PA200 has two openings formed by numerous positively charged residues that respectively bind (5,6)-bisdiphosphoinositol tetrakisphosphate (5,6[PP]2-InsP4) and inositol hexakisphosphate (InsP6) and are likely to be the gates that lead unfolded proteins through PA200 and into the 20S. Besides, our structural analysis of PA200 found that the bromodomain (BRD)-like (BRDL) domain of PA200 shows considerable sequence variation in comparison to other human BRDs, as it contains only 82 residues because of a short ZA loop, and cannot be classified into any of the eight typical human BRD families. Taken together, the results obtained from this study provide important insights into human PA200-induced 20S gate opening for substrate degradation and the opportunities to explore the mechanism for its recognition of H4 histone in acetylation-mediated proteasomal degradation. | ||
| - | + | Cryo-EM structures of the human PA200 and PA200-20S complex reveal regulation of proteasome gate opening and two PA200 apertures.,Guan H, Wang Y, Yu T, Huang Y, Li M, Saeed AFUH, Perculija V, Li D, Xiao J, Wang D, Zhu P, Ouyang S PLoS Biol. 2020 Mar 5;18(3):e3000654. doi: 10.1371/journal.pbio.3000654., eCollection 2020 Mar. PMID:32134919<ref>PMID:32134919</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | [[Category: | + | <div class="pdbe-citations 6kwx" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Hongxin, G]] | [[Category: Hongxin, G]] | ||
| + | [[Category: Ouyang, S]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Proteasome activator]] | ||
Revision as of 09:07, 1 April 2020
cryo-EM structure of human PA200
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