Structural highlights
Function
[UBB_HUMAN] 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.[1] [2]
Publication Abstract from PubMed
Ubiquitin phosphorylation is emerging as an important regulatory layer in the ubiquitin system. This is exemplified by the phosphorylation of ubiquitin on Serine 65 by the Parkinson's disease-associated kinase PINK1 that mediates the activation of the E3 ligase Parkin. Additional phosphorylation sites on ubiquitin have been identified that may also have important cellular roles. Here we report a versatile strategy for preparing phosphorylated ubiquitin. We biochemically and structurally characterize semisynthetic Ser65-phospho-ubiquitin. Unexpectedly, we observed disulphide bond formation between ubiquitin molecules giving rise to a novel crystal form for ubiquitin. The technologies outlined provide a direct approach to study combinatorial effects of phosphorylation on ubiquitin function. Our analysis also suggests that disulphide engineering of ubiquitin could be a useful strategy for obtaining alternative crystal forms of ubiquitin species thereby facilitating structural validation.
A Versatile Strategy for the Semisynthetic Production of Ser65 Phosphorylated Ubiquitin and its Biochemical and Structural Characterization.,Han C, Pao KC, Kazlauskaite A, Muqit MM, Virdee S Chembiochem. 2015 May 22. doi: 10.1002/cbic.201500185. PMID:26010437[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
- ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
- ↑ Han C, Pao KC, Kazlauskaite A, Muqit MM, Virdee S. A Versatile Strategy for the Semisynthetic Production of Ser65 Phosphorylated Ubiquitin and its Biochemical and Structural Characterization. Chembiochem. 2015 May 22. doi: 10.1002/cbic.201500185. PMID:26010437 doi:http://dx.doi.org/10.1002/cbic.201500185
