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6m3i
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Crystal structure of HPF1/PARP1 complex== |
| - | <StructureSection load='6m3i' size='340' side='right'caption='[[6m3i]]' scene=''> | + | <StructureSection load='6m3i' size='340' side='right'caption='[[6m3i]], [[Resolution|resolution]] 1.98Å' 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'>[[6m3i]] is a 2 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=6M3I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M3I 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=6m3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m3i OCA], [https://pdbe.org/6m3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m3i RCSB], [https://www.ebi.ac.uk/pdbsum/6m3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m3i ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.98Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UNU:BENZAMIDE'>UNU</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=6m3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m3i OCA], [https://pdbe.org/6m3i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m3i RCSB], [https://www.ebi.ac.uk/pdbsum/6m3i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m3i ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HPF1_HUMAN HPF1_HUMAN] Acts as a cofactor for serine ADP-ribosylation by conferring serine specificity on PARP1 and PARP2: interacts with PARP1 and PARP2 and is able to change amino acid specificity toward serine (PubMed:28190768, PubMed:29480802). Promotes histone serine ADP-ribosylation in response to DNA damage, limiting DNA damage-induced PARP1 hyper-automodification, and ensuring genome stability (PubMed:27067600, PubMed:28190768). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:29480802). HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1 (PubMed:30257210).<ref>PMID:27067600</ref> <ref>PMID:28190768</ref> <ref>PMID:29480802</ref> <ref>PMID:30257210</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Upon binding to DNA breaks, poly(ADP-ribose) polymerase 1 (PARP1) ADP-ribosylates itself and other factors to initiate DNA repair. Serine is the major residue for ADP-ribosylation upon DNA damage, which strictly depends on HPF1. Here, we report the crystal structures of human HPF1/PARP1-CAT DeltaHD complex at 1.98 A resolution, and mouse and human HPF1 at 1.71 A and 1.57 A resolution, respectively. Our structures and mutagenesis data confirm that the structural insights obtained in a recent HPF1/PARP2 study by Suskiewicz et al. apply to PARP1. Moreover, we quantitatively characterize the key residues necessary for HPF1/PARP1 binding. Our data show that through salt-bridging to Glu284/Asp286, Arg239 positions Glu284 to catalyze serine ADP-ribosylation, maintains the local conformation of HPF1 to limit PARP1 automodification, and facilitates HPF1/PARP1 binding by neutralizing the negative charge of Glu284. These findings, along with the high-resolution structural data, may facilitate drug discovery targeting PARP1. | ||
| + | |||
| + | HPF1 remodels the active site of PARP1 to enable the serine ADP-ribosylation of histones.,Sun FH, Zhao P, Zhang N, Kong LL, Wong CCL, Yun CH Nat Commun. 2021 Feb 15;12(1):1028. doi: 10.1038/s41467-021-21302-4. PMID:33589610<ref>PMID:33589610</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6m3i" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Sun FH]] |
| + | [[Category: Yun CH]] | ||
Current revision
Crystal structure of HPF1/PARP1 complex
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