8zu6
From Proteopedia
(Difference between revisions)
m (Protected "8zu6" [edit=sysop:move=sysop]) |
|||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Solution NMR Structure of PACT D3 Homodimer== | |
| + | <StructureSection load='8zu6' size='340' side='right'caption='[[8zu6]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8zu6]] is a 2 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=8ZU6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ZU6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 15 models</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=8zu6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8zu6 OCA], [https://pdbe.org/8zu6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8zu6 RCSB], [https://www.ebi.ac.uk/pdbsum/8zu6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8zu6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN] Defects in PRKRA are the cause of dystonia type 16 (DYT16) [MIM:[https://omim.org/entry/612067 612067]. DYT16 is an early-onset dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT16 patients have progressive, generalized dystonia with axial muscle involvement, oro-mandibular (sardonic smile) and laryngeal dystonia and, in some cases, parkinsonian features.<ref>PMID:18243799</ref> <ref>PMID:18420150</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PRKRA_HUMAN PRKRA_HUMAN] Activates EIF2AK2/PKR in the absence of double stranded RNA (dsRNA), leading to phosphorylation of EIF2S1/EFI2-alpha and inhibition of translation and induction of apoptosis. Required for siRNA production by DICER1 and for subsequent siRNA-mediated post-transcriptional gene silencing. Does not seem to be required for processing of pre-miRNA to miRNA by DICER1.<ref>PMID:9687506</ref> <ref>PMID:10336432</ref> <ref>PMID:11238927</ref> <ref>PMID:16424907</ref> <ref>PMID:16982605</ref> <ref>PMID:17452327</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The innate immune sensor PKR for double-stranded RNA (dsRNA) is critical for antiviral defense, but its aberrant activation by cellular dsRNA is linked to various diseases. The dsRNA-binding protein PACT plays a critical yet controversial role in this pathway. We show that PACT directly suppresses PKR activation by endogenous dsRNA ligands, such as inverted-repeat Alu RNAs, which robustly activate PKR in the absence of PACT. Instead of competing for dsRNA binding, PACT prevents PKR from scanning along dsRNA-a necessary step for PKR molecules to encounter and phosphorylate each other for activation. While PKR favors longer dsRNA for increased co-occupancy and scanning-mediated activation, longer dsRNA is also more susceptible to PACT-mediated regulation due to increased PACT-PKR co-occupancy. Unlike viral inhibitors that constitutively suppress PKR, this RNA-dependent mechanism allows PACT to fine-tune PKR activation based on dsRNA length and quantity, ensuring self-tolerance without sequestering most cellular dsRNA. | ||
| - | + | PACT prevents aberrant activation of PKR by endogenous dsRNA without sequestration.,Ahmad S, Zou T, Hwang J, Zhao L, Wang X, Davydenko A, Buchumenski I, Zhuang P, Fishbein AR, Capcha-Rodriguez D, Orgel A, Levanon EY, Myong S, Chou J, Meyerson M, Hur S Nat Commun. 2025 Apr 8;16(1):3325. doi: 10.1038/s41467-025-58433-x. PMID:40199855<ref>PMID:40199855</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8zu6" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ahmad S]] | ||
| + | [[Category: Chou J]] | ||
| + | [[Category: Hur S]] | ||
| + | [[Category: Zhao L]] | ||
Current revision
Solution NMR Structure of PACT D3 Homodimer
| |||||||||||
Categories: Homo sapiens | Large Structures | Ahmad S | Chou J | Hur S | Zhao L
