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From Proteopedia
Crystal structure of K33 linked di-Ubiquitin
Structural highlights
Function[UBC_BOVIN] Ubiquitin: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Publication Abstract from PubMedUbiquitylation regulates a multitude of biological processes and this versatility stems from the ability of ubiquitin to form topologically different polymers of eight different linkage types. While some linkages have been studied in detail, other linkage types including Lys33-linked polyubiquitin are poorly understood. Here we identify an enzymatic system for the large-scale assembly of Lys33 chains by combining the HECT (homologous to the E6-AP carboxyl terminus) E3 ligase AREL1 (apoptosis-resistant E3 ubiquitin protein ligase 1) with linkage selective deubiquitinases (DUBs). Moreover, this first characterisation of the chain selectivity of AREL1 indicates its preference for assembling Lys33- and Lys11-linked ubiquitin chains. Intriguingly, the crystal structure of Lys33-linked diubiquitin (diUb) reveals that it adopts a compact conformation very similar to that observed for Lys11-linked diUb. In contrast, crystallographic analysis of Lys33-linked triUb reveals a more extended conformation. These two distinct conformational states of Lys33-linked polyUb may be selectively recognized by ubiquitin binding domains and enzymes of the ubiquitin system. Importantly, our work provides a method to assemble Lys33-linked polyubiquitin that will allow further characterization of this atypical chain type. Assembly and structure of Lys33-linked polyubiquitin reveals distinct conformations.,Kristariyanto YA, Choi SY, Abdul Rehman SA, Ritorto MS, Campbell DG, Morrice NA, Toth R, Kulathu Y Biochem J. 2015 Feb 27. PMID:25723849[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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