8rxb

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "8rxb" [edit=sysop:move=sysop])
Current revision (05:22, 15 May 2024) (edit) (undo)
 
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 8rxb is ON HOLD until Paper Publication
+
==Human UPF1 CH domain in complex with SMG6 peptide==
 +
<StructureSection load='8rxb' size='340' side='right'caption='[[8rxb]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[8rxb]] is a 12 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=8RXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RXB 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]] 2.6&#8491;</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=8rxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rxb OCA], [https://pdbe.org/8rxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rxb RCSB], [https://www.ebi.ac.uk/pdbsum/8rxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rxb ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/RENT1_HUMAN RENT1_HUMAN] RNA-dependent helicase and ATPase required for nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited to mRNAs upon translation termination and undergoes a cycle of phosphorylation and dephosphorylation; its phosphorylation appears to be a key step in NMD. Recruited by release factors to stalled ribosomes together with the SMG1C protein kinase complex to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) (located 50-55 or more nucleotides downstream from the termination codon) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Phosphorylated UPF1 is recognized by EST1B/SMG5, SMG6 and SMG7 which are thought to provide a link to the mRNA degradation machinery involving exonucleolytic and endonucleolytic pathways, and to serve as adapters to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation and allowing the recycling of NMD factors. UPF1 can also activate NMD without UPF2 or UPF3, and in the absence of the NMD-enhancing downstream EJC indicative for alternative NMD pathways. Plays a role in replication-dependent histone mRNA degradation at the end of phase S; the function is independent of UPF2. For the recognition of premature termination codons (PTC) and initiation of NMD a competitive interaction between UPF1 and PABPC1 with the ribosome-bound release factors is proposed. The ATPase activity of UPF1 is required for disassembly of mRNPs undergoing NMD. Essential for embryonic viability.<ref>PMID:11163187</ref> <ref>PMID:16086026</ref> <ref>PMID:18172165</ref> <ref>PMID:21145460</ref> <ref>PMID:21419344</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Nonsense-mediated mRNA decay (NMD) is a conserved co-translational mRNA surveillance and turnover pathway across eukaryotes. NMD has a central role in degrading defective mRNAs and also regulates the stability of a significant portion of the transcriptome. The pathway is organized around UPF1, an RNA helicase that can interact with several NMD-specific factors. In human cells, degradation of the targeted mRNAs begins with a cleavage event that requires the recruitment of the SMG6 endonuclease to UPF1. Previous studies have identified functional links between SMG6 and UPF1, but the underlying molecular mechanisms have remained elusive. Here, we used mass spectrometry, structural biology and biochemical approaches to identify and characterize a conserved short linear motif in SMG6 that interacts with the cysteine/histidine-rich (CH) domain of UPF1. Unexpectedly, we found that the UPF1-SMG6 interaction is precluded when the UPF1 CH domain is engaged with another NMD factor, UPF2. Based on cryo-EM data, we propose that the formation of distinct SMG6-containing and UPF2-containing NMD complexes may be dictated by different conformational states connected to the RNA-binding status of UPF1. Our findings rationalize a key event in metazoan NMD and advance our understanding of mechanisms regulating activity and guiding substrate recognition by the SMG6 endonuclease.
-
Authors: Langer, L., Basquin, J., Conti, E.
+
UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2.,Langer LM, Kurscheidt K, Basquin J, Bonneau F, Iermak I, Basquin C, Conti E Nucleic Acids Res. 2024 May 6:gkae323. doi: 10.1093/nar/gkae323. PMID:38709891<ref>PMID:38709891</ref>
-
Description: Human UPF1 CH domain in complex with SMG6 peptide
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
-
[[Category: Conti, E]]
+
<div class="pdbe-citations 8rxb" style="background-color:#fffaf0;"></div>
-
[[Category: Langer, L]]
+
== References ==
-
[[Category: Basquin, J]]
+
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Basquin J]]
 +
[[Category: Conti E]]
 +
[[Category: Langer L]]

Current revision

Human UPF1 CH domain in complex with SMG6 peptide

PDB ID 8rxb

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8rxb"
Personal tools