7yab: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7yab]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YAB FirstGlance]. <br> | <table><tr><td colspan='2'>[[7yab]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YAB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YAB FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7yab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yab OCA], [https://pdbe.org/7yab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yab RCSB], [https://www.ebi.ac.uk/pdbsum/7yab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yab 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=7yab FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yab OCA], [https://pdbe.org/7yab PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yab RCSB], [https://www.ebi.ac.uk/pdbsum/7yab PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yab ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ZFAN1_HUMAN ZFAN1_HUMAN] Plays a role in the regulation of cytoplasmic stress granules (SGs) turnover. SGs are dynamic and transient cytoplasmic ribonucleoprotein assemblies important for cellular protein homeostasis when protein production is suspended after acute exogenous stress (PubMed:29804830). Associates with SGs and is involved in the efficient and specific arsenite-induced clearance process of SGs through the recruitment of the ubiquitin-selective ATPase VCP and the 26S proteasome (PubMed:29804830). This process requires both complexes for efficient degradation of damaged ubiquitinated SG proteins during recovery from arsenite stress, and hence avoiding aberrant cytoplasmic SGs degradation via autophagy (PubMed:29804830).<ref>PMID:29804830</ref> | [https://www.uniprot.org/uniprot/ZFAN1_HUMAN ZFAN1_HUMAN] Plays a role in the regulation of cytoplasmic stress granules (SGs) turnover. SGs are dynamic and transient cytoplasmic ribonucleoprotein assemblies important for cellular protein homeostasis when protein production is suspended after acute exogenous stress (PubMed:29804830). Associates with SGs and is involved in the efficient and specific arsenite-induced clearance process of SGs through the recruitment of the ubiquitin-selective ATPase VCP and the 26S proteasome (PubMed:29804830). This process requires both complexes for efficient degradation of damaged ubiquitinated SG proteins during recovery from arsenite stress, and hence avoiding aberrant cytoplasmic SGs degradation via autophagy (PubMed:29804830).<ref>PMID:29804830</ref> | ||
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== Publication Abstract from PubMed == | |||
Arsenite-induced stress granule (SG) formation can be cleared by the ubiquitin-proteasome system aided by the ATP-dependent unfoldase p97. ZFAND1 participates in this pathway by recruiting p97 to trigger SG clearance. ZFAND1 contains two An1-type zinc finger domains (ZF1 and ZF2), followed by a ubiquitin-like domain (UBL); but their structures are not experimentally determined. To shed light on the structural basis of the ZFAND1-p97 interaction, we determined the atomic structures of the individual domains of ZFAND1 by solution-state NMR spectroscopy and X-ray crystallography. We further characterized the interaction between ZFAND1 and p97 by methyl NMR spectroscopy and cryo-EM. (15)N spin relaxation dynamics analysis indicated independent domain motions for ZF1, ZF2, and UBL. The crystal structure and NMR structure of UBL showed a conserved beta-grasp fold homologous to ubiquitin and other UBLs. Nevertheless, the UBL of ZFAND1 contains an additional N-terminal helix that adopts different conformations in the crystalline and solution states. ZFAND1 uses the C-terminal UBL to bind to p97, evidenced by the pronounced line-broadening of the UBL domain during the p97 titration monitored by methyl NMR spectroscopy. ZFAND1 binding induces pronounced conformational heterogeneity in the N-terminal domain of p97, leading to a partial loss of the cryo-EM density of the N-terminal domain of p97. In conclusion, this work paved the way for a better understanding of the interplay between p97 and ZFAND1 in the context of SG clearance. | |||
Structural insight into the ZFAND1-p97 interaction involved in stress granule clearance.,Lai CH, Ko KT, Fan PJ, Yu TA, Chang CF, Draczkowski P, Hsu SD J Biol Chem. 2024 May;300(5):107230. doi: 10.1016/j.jbc.2024.107230. Epub 2024 , Mar 25. PMID:38537699<ref>PMID:38537699</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
<references/> | <references/> | ||