7px3: Difference between revisions
No edit summary |
No edit summary |
||
| (One intermediate revision by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of U5 snRNP assembly and recycling factor TSSC4 in complex with BRR2 and Jab1 domain of PRPF8== | |||
<StructureSection load='7px3' size='340' side='right'caption='[[7px3]], [[Resolution|resolution]] 3.05Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7px3]] is a 3 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=7PX3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PX3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.05Å</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=7px3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7px3 OCA], [https://pdbe.org/7px3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7px3 RCSB], [https://www.ebi.ac.uk/pdbsum/7px3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7px3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TSSC4_HUMAN TSSC4_HUMAN] Protein associated with the U5 snRNP, during its maturation and its post-splicing recycling and which is required for spliceosomal tri-snRNP complex assembly in the nucleus (PubMed:34131137, PubMed:35188580). Has a molecular sequestering activity and transiently hinders SNRNP200 binding sites for constitutive splicing factors that intervene later during the assembly of the spliceosome and splicing (PubMed:35188580). Together with its molecular sequestering activity, may also function as a molecular adapter and placeholder, coordinating the assembly of the U5 snRNP and its association with the U4/U6 di-snRNP (PubMed:34131137).<ref>PMID:34131137</ref> <ref>PMID:35188580</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4's intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites. It thereby inhibits SNRNP200 helicase activity, spatially aligns the proteins, coordinates formation of a U5 sub-module and transiently blocks premature interaction of SNRNP200 with at least three other spliceosomal factors. Guided by the structure, we designed a TSSC4 variant that lacks stable binding to the PRPF8 Jab1/MPN domain or SNRNP200 in vitro. Comparative immunoprecipitation/mass spectrometry from HEK293 nuclear extract revealed distinct interaction profiles of wild type TSSC4 and the variant deficient in PRPF8/SNRNP200 binding with snRNP proteins, other spliceosomal proteins as well as snRNP assembly/recycling factors and chaperones. Our findings elucidate molecular strategies employed by an intrinsically disordered protein to promote snRNP assembly, and suggest multiple TSSC4-dependent stages during snRNP assembly/recycling. | |||
The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling.,Bergfort A, Hilal T, Kuropka B, Ilik IA, Weber G, Aktas T, Freund C, Wahl MC Nucleic Acids Res. 2022 Mar 21;50(5):2938-2958. doi: 10.1093/nar/gkac087. PMID:35188580<ref>PMID:35188580</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7px3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Helicase 3D structures|Helicase 3D structures]] | |||
*[[Nucleoprotein 3D structures|Nucleoprotein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Aktas T]] | |||
[[Category: Bergfort A]] | |||
[[Category: Freund C]] | |||
[[Category: Hilal T]] | |||
[[Category: Ilik IA]] | |||
[[Category: Kuropka B]] | |||
[[Category: Wahl MC]] | |||
[[Category: Weber G]] | |||