2y5b

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Structure of USP21 in complex with linear diubiquitin-aldehydeStructure of USP21 in complex with linear diubiquitin-aldehyde

Structural highlights

2y5b is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.7Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP21_HUMAN Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation. Regulates gene expression via histone H2A deubiquitination (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates.[1]

Publication Abstract from PubMed

Modification of proteins by ubiquitin (Ub) and Ub-like (Ubl) modifiers regulates a variety of cellular functions. The ability of Ub to form chains of eight structurally and functionally distinct types adds further complexity to the system. Ub-specific proteases (USPs) hydrolyse polyUb chains, and some have been suggested to be cross-reactive with Ubl modifiers, such as neural precursor cell expressed, developmentally downregulated 8 (NEDD8) and interferon-stimulated gene 15 (ISG15). Here, we report that USP21 cleaves Ub polymers, and with reduced activity also targets ISG15, but is inactive against NEDD8. A crystal structure of USP21 in complex with linear diUb aldehyde shows how USP21 interacts with polyUb through a previously unidentified second Ub- and ISG15-binding surface on the USP domain core. We also rationalize the inability of USP21 to target NEDD8 and identify differences that allow USPs to distinguish between structurally related modifications.

Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21.,Ye Y, Akutsu M, Reyes-Turcu F, Enchev RI, Wilkinson KD, Komander D EMBO Rep. 2011 Apr;12(4):350-7. Epub 2011 Mar 11. PMID:21399617[2]

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

See Also

References

  1. Gong L, Kamitani T, Millas S, Yeh ET. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins. J Biol Chem. 2000 May 12;275(19):14212-6. PMID:10799498
  2. Ye Y, Akutsu M, Reyes-Turcu F, Enchev RI, Wilkinson KD, Komander D. Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21. EMBO Rep. 2011 Apr;12(4):350-7. Epub 2011 Mar 11. PMID:21399617 doi:10.1038/embor.2011.17

2y5b, resolution 2.70Å

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