|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6kwx' size='340' side='right'caption='[[6kwx]], [[Resolution|resolution]] 3.75Å' scene=''> | | <StructureSection load='6kwx' size='340' side='right'caption='[[6kwx]], [[Resolution|resolution]] 3.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6kwx]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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://proteopedia.org/fgij/fg.htm?mol=6KWX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6kwx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6KWX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PSME4, KIAA0077 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</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://proteopedia.org/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> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6kwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kwx OCA], [https://pdbe.org/6kwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kwx RCSB], [https://www.ebi.ac.uk/pdbsum/6kwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kwx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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> | + | [https://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>
| + | |
| - | <div class="pdbe-citations 6kwx" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hongxin, G]] | + | [[Category: Hongxin G]] |
| - | [[Category: Ouyang, S]] | + | [[Category: Ouyang S]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Proteasome activator]]
| + | |
| Structural highlights
Function
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.[1] [2] [3] [4]
References
- ↑ Ustrell V, Hoffman L, Pratt G, Rechsteiner M. PA200, a nuclear proteasome activator involved in DNA repair. EMBO J. 2002 Jul 1;21(13):3516-25. doi: 10.1093/emboj/cdf333. PMID:12093752 doi:http://dx.doi.org/10.1093/emboj/cdf333
- ↑ Blickwedehl J, Agarwal M, Seong C, Pandita RK, Melendy T, Sung P, Pandita TK, Bangia N. Role for proteasome activator PA200 and postglutamyl proteasome activity in genomic stability. Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16165-70. doi:, 10.1073/pnas.0803145105. Epub 2008 Oct 9. PMID:18845680 doi:http://dx.doi.org/10.1073/pnas.0803145105
- ↑ Blickwedehl J, Olejniczak S, Cummings R, Sarvaiya N, Mantilla A, Chanan-Khan A, Pandita TK, Schmidt M, Thompson CB, Bangia N. The proteasome activator PA200 regulates tumor cell responsiveness to glutamine and resistance to ionizing radiation. Mol Cancer Res. 2012 Jul;10(7):937-44. doi: 10.1158/1541-7786.MCR-11-0493-T. Epub, 2012 May 1. PMID:22550082 doi:http://dx.doi.org/10.1158/1541-7786.MCR-11-0493-T
- ↑ Qian MX, Pang Y, Liu CH, Haratake K, Du BY, Ji DY, Wang GF, Zhu QQ, Song W, Yu Y, Zhang XX, Huang HT, Miao S, Chen LB, Zhang ZH, Liang YN, Liu S, Cha H, Yang D, Zhai Y, Komatsu T, Tsuruta F, Li H, Cao C, Li W, Li GH, Cheng Y, Chiba T, Wang L, Goldberg AL, Shen Y, Qiu XB. Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis. Cell. 2013 May 23;153(5):1012-24. doi: 10.1016/j.cell.2013.04.032. PMID:23706739 doi:http://dx.doi.org/10.1016/j.cell.2013.04.032
|
