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4wlp

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Revision as of 08:40, 4 December 2019

Crystal structure of UCH37-NFRKB Inhibited Deubiquitylating Complex

Structural highlights

4wlp is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4wlq, 4wlr
Gene:	UCHL5, UCH37, AD-019, CGI-70 (HUMAN), NFRKB, INO80G (HUMAN)
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UCHL5_HUMAN] Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.^[1] ^[2] [NFRKB_HUMAN] Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'.^[3] Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex.^[4]

Publication Abstract from PubMed

The UCH37 deubiquitylase functions in two large and very different complexes, the 26S proteasome and the INO80 chromatin remodeler. We have performed biochemical characterization and determined crystal structures of UCH37 in complexes with RPN13 and NFRKB, which mediate its recruitment to the proteasome and INO80, respectively. RPN13 and NFRKB make similar contacts to the UCH37 C-terminal domain but quite different contacts to the catalytic UCH domain. RPN13 can activate UCH37 by disrupting dimerization, although physiologically relevant activation likely results from stabilization of a surface competent for ubiquitin binding and modulation of the active-site crossover loop. In contrast, NFRKB inhibits UCH37 by blocking the ubiquitin-binding site and by disrupting the enzyme active site. These findings reveal remarkable commonality in mechanisms of recruitment, yet very different mechanisms of regulating enzyme activity, and provide a foundation for understanding the roles of UCH37 in the unrelated proteasome and INO80 complexes.

Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase.,VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP Mol Cell. 2015 Mar 5;57(5):901-11. doi: 10.1016/j.molcel.2015.01.016. Epub 2015, Feb 19. PMID:25702872^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yao T, Song L, Xu W, DeMartino GN, Florens L, Swanson SK, Washburn MP, Conaway RC, Conaway JW, Cohen RE. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol. 2006 Sep;8(9):994-1002. Epub 2006 Aug 13. PMID:16906146 doi:ncb1460
↑ Yao T, Song L, Jin J, Cai Y, Takahashi H, Swanson SK, Washburn MP, Florens L, Conaway RC, Cohen RE, Conaway JW. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol Cell. 2008 Sep 26;31(6):909-17. doi: 10.1016/j.molcel.2008.08.027. PMID:18922472 doi:10.1016/j.molcel.2008.08.027
↑ Yao T, Song L, Jin J, Cai Y, Takahashi H, Swanson SK, Washburn MP, Florens L, Conaway RC, Cohen RE, Conaway JW. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol Cell. 2008 Sep 26;31(6):909-17. doi: 10.1016/j.molcel.2008.08.027. PMID:18922472 doi:10.1016/j.molcel.2008.08.027
↑ Yao T, Song L, Jin J, Cai Y, Takahashi H, Swanson SK, Washburn MP, Florens L, Conaway RC, Cohen RE, Conaway JW. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol Cell. 2008 Sep 26;31(6):909-17. doi: 10.1016/j.molcel.2008.08.027. PMID:18922472 doi:10.1016/j.molcel.2008.08.027
↑ VanderLinden RT, Hemmis CW, Schmitt B, Ndoja A, Whitby FG, Robinson H, Cohen RE, Yao T, Hill CP. Structural Basis for the Activation and Inhibition of the UCH37 Deubiquitylase. Mol Cell. 2015 Mar 5;57(5):901-11. doi: 10.1016/j.molcel.2015.01.016. Epub 2015, Feb 19. PMID:25702872 doi:http://dx.doi.org/10.1016/j.molcel.2015.01.016

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wlp"

@@ Line 1: / Line 1: @@
 ==Crystal structure of UCH37-NFRKB Inhibited Deubiquitylating Complex==
-<StructureSection load='4wlp' size='340' side='right' caption='[[4wlp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+<StructureSection load='4wlp' size='340' side='right'caption='[[4wlp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4wlp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WLP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WLP FirstGlance]. <br>
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 4wlp" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Thioesterase|Thioesterase]]
 == References ==
 <references/>
@@ Line 25: / Line 28: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ubiquitinyl hydrolase 1]]
 [[Category: Hemmis, C W]]

4wlp

From Proteopedia

Revision as of 08:40, 4 December 2019

Crystal structure of UCH37-NFRKB Inhibited Deubiquitylating Complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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