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6m3h
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of mouse HPF1== | |
| + | <StructureSection load='6m3h' size='340' side='right'caption='[[6m3h]], [[Resolution|resolution]] 1.71Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6m3h]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M3H FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.71Å</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=6m3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m3h OCA], [https://pdbe.org/6m3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m3h RCSB], [https://www.ebi.ac.uk/pdbsum/6m3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m3h ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HPF1_MOUSE HPF1_MOUSE] Cofactor for serine ADP-ribosylation that confers serine specificity on PARP1 and PARP2 and plays a key role in DNA damage response. Initiates the repair of double-strand DNA breaks: recruited to DNA damage sites by PARP1 and PARP2 and switches the amino acid specificity of PARP1 and PARP2 from aspartate or glutamate to serine residues, licensing serine ADP-ribosylation of target proteins. Serine ADP-ribosylation of target proteins, such as histones, promotes decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. HPF1 acts by completing the active site of PARP1 and PARP2: forms a composite active site composed of residues from HPF1 and PARP1 or PARP2. While HPF1 promotes the initiation of serine ADP-ribosylation, it restricts the polymerase activity of PARP1 and PARP2 in order to limit the length of poly-ADP-ribose chains. HPF1 also promotes tyrosine ADP-ribosylation, probably by conferring tyrosine specificity on PARP1.[UniProtKB:Q9NWY4] | ||
| + | <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> | |
| - | [[Category: | + | </div> |
| - | [[Category: Sun | + | <div class="pdbe-citations 6m3h" style="background-color:#fffaf0;"></div> |
| - | [[Category: Yun | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Sun FH]] | ||
| + | [[Category: Yun CH]] | ||
Current revision
Crystal structure of mouse HPF1
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