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tisdag 3 juli 2018

USP15 omaa funktionaalisen Zn-finger rakenteen.

 Huomasin että USp 5 sisältää kryptisen Zn-finger kohdan. etsin yleistietoa, josi useissa USP molekyleissä olisi Zn- finger ja löysin tämän USP 15. sen takia se tulee tässä välillä. Zn-fingger rakenne on sen funktioissa essentielli ja vaikutata hienosäätöä ubikitinaatio alueella  polyubikitinoitujen koostumien käsittelyssä.  samalla se stabilisoi erään E3 ubikigiiniligaasin. katson myös tämän E3 ligaasin ominaisuuksia.

https://www.ncbi.nlm.nih.gov/pubmed/16005295
Curr Biol. 2005 Jul 12;15(13):1217-21.
The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1.
The COP9 signalosome (CSN) is a conserved protein complex found in all eukaryotic cells and involved in the regulation of the ubiquitin (Ub)/26S proteasome system. It binds numerous proteins, including the Ub E3 ligases and the deubiquitinating enzyme Ubp12p, the S. pombe ortholog of human USP15. We found that USP15 copurified with the human CSN complex. Isolated CSN complex exhibited protease activity that deubiquitinated poly-Ub substrates and was completely inhibited by o-phenanthroline (OPT), a metal-chelating agent. Surprisingly, the recombinant USP15 was also not able to cleave isopeptide bonds of poly-Ub chains in presence of OPT. Detailed analysis of USP sequences led to the discovery of a novel zinc (Zn) finger in USP15 and related USPs. Mutation of a single conserved cysteine residue in the predicted Zn binding motif resulted in the loss of USP15 capability to degrade poly-Ub substrates, indicating that the Zn finger is essential for the cleavage of poly-Ub chains. Moreover, pulldown experiments demonstrated diminished binding of tetra-Ub to mutated USP15. Cotransfection of USP15 and the Ub ligase Rbx1 revealed that the wild-type deubiquitinating enzyme, but not the USP15 mutant with a defective Zn finger, stabilized Rbx1 toward the Ub system, most likely by reversing poly/autoubiquitination. In summary, a functional Zn finger of USP15 is needed to maintain a conformation essential for disassembling poly-Ub chains, a prerequisite for rescuing the E3 ligase Rbx1.
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Geeni  USP ( 12q14.1) Also known asUNPH4; UNPH-2
Summary  This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]
Expression Ubiquitous expression in bone marrow (RPKM 16.1), appendix (RPKM 8.0) and 24 other
Preferred Names  ubiquitin carboxyl-terminal hydrolase 15
Names
deubiquitinating enzyme 15
ubiquitin thioesterase 15
ubiquitin thiolesterase 15
ubiquitin-specific-processing protease 15
 https://www.ncbi.nlm.nih.gov/protein/NP_001239007.1

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