7otq
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Cryo-EM structure of ALC1/CHD1L bound to a PARylated nucleosome== |
| - | <StructureSection load='7otq' size='340' side='right'caption='[[7otq]]' scene=''> | + | <StructureSection load='7otq' size='340' side='right'caption='[[7otq]], [[Resolution|resolution]] 4.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7otq]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7OTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OTQ FirstGlance]. <br> |
| - | </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=7otq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7otq OCA], [https://pdbe.org/7otq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7otq RCSB], [https://www.ebi.ac.uk/pdbsum/7otq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7otq ProSAT]</span></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]] 4.8Å</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=7otq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7otq OCA], [https://pdbe.org/7otq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7otq RCSB], [https://www.ebi.ac.uk/pdbsum/7otq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7otq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CHD1L_HUMAN CHD1L_HUMAN] ATP-dependent chromatin remodeler that mediates chromatin-remodeling following DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:33357431, PubMed:34210977, PubMed:34486521, PubMed:34874266). Recruited to DNA damage sites through interaction with poly-ADP-ribose: specifically recognizes and binds histones that are poly-ADP-ribosylated on serine residues in response to DNA damage (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Poly-ADP-ribose-binding activates the ATP-dependent chromatin remodeler activity, thereby regulating chromatin during DNA repair (PubMed:19661379, PubMed:29220652, PubMed:29220653, PubMed:34486521, PubMed:34874266). Catalyzes nucleosome sliding away from DNA breaks in an ATP-dependent manner (PubMed:19661379, PubMed:29220652, PubMed:29220653). Chromatin remodeling activity promotes PARP2 removal from chromatin (PubMed:33275888).<ref>PMID:19661379</ref> <ref>PMID:29220652</ref> <ref>PMID:29220653</ref> <ref>PMID:33275888</ref> <ref>PMID:33357431</ref> <ref>PMID:34210977</ref> <ref>PMID:34486521</ref> <ref>PMID:34874266</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The chromatin remodeler ALC1 is recruited to and activated by DNA damage-induced poly(ADP-ribose) (PAR) chains deposited by PARP1/PARP2/HPF1 upon detection of DNA lesions. ALC1 has emerged as a candidate drug target for cancer therapy as its loss confers synthetic lethality in homologous recombination-deficient cells. However, structure-based drug design and molecular analysis of ALC1 have been hindered by the requirement for PARylation and the highly heterogeneous nature of this post-translational modification. Here, we reconstituted an ALC1 and PARylated nucleosome complex modified in vitro using PARP2 and HPF1. This complex was amenable to cryo-EM structure determination without cross-linking, which enabled visualization of several intermediate states of ALC1 from the recognition of the PARylated nucleosome to the tight binding and activation of the remodeler. Functional biochemical assays with PARylated nucleosomes highlight the importance of nucleosomal epitopes for productive remodeling and suggest that ALC1 preferentially slides nucleosomes away from DNA breaks. | ||
| + | |||
| + | Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome.,Bacic L, Gaullier G, Sabantsev A, Lehmann LC, Brackmann K, Dimakou D, Halic M, Hewitt G, Boulton SJ, Deindl S Elife. 2021 Sep 6;10:e71420. doi: 10.7554/eLife.71420. PMID:34486521<ref>PMID:34486521</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7otq" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Chromodomain-helicase-DNA-binding protein 3D structures|Chromodomain-helicase-DNA-binding protein 3D structures]] | ||
| + | *[[Histone 3D structures|Histone 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Xenopus laevis]] | ||
| + | [[Category: Bacic L]] | ||
| + | [[Category: Deindl S]] | ||
| + | [[Category: Gaullier G]] | ||
Current revision
Cryo-EM structure of ALC1/CHD1L bound to a PARylated nucleosome
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