6if1 | pdb_00006if1
Crystal structure of Ube2K and K48-linked di-ubiquitin complex
Structural highlights
FunctionUBE2K_HUMAN Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.[1] [2] [3] [4] [5] [6] [7] [8] Publication Abstract from PubMedUbiquitin-conjugating enzymes (E2) form thioester bonds with ubiquitin (Ub), which are subsequently transferred to target proteins for cellular progress. Ube2K/E2-25K (a class II E2 enzyme) contains a C-terminal ubiquitin-associated (UBA) domain that has been suggested to control ubiquitin recognition, dimerization, or poly-ubiquitin chain formation. Ube2K is a special E2 because it synthesizes K48-linked poly-ubiquitin chains without E3 ubiquitin ligase. We found that a novel interaction between the acceptor di-Ub (Ub(2)) and the auxiliary Ube2K promotes the discharging reaction and production of tri-Ub (Ub(3)), probably by guiding and positioning the K48 (in the distal Ub) of the acceptor Ub(2) in the active site. We also determined the crystal structure of Ube2K-Ub(2) at 2.47â¯A resolution. Based on our structural and biochemical data, we proposed a structural model of Ub(3) synthesis by Ube2K without E3. Crystal structure of the Ube2K/E2-25K and K48-linked di-ubiquitin complex provides structural insight into the mechanism of K48-specific ubiquitin chain synthesis.,Lee JG, Youn HS, Kang JY, Park SY, Kidera A, Yoo YJ, Eom SH Biochem Biophys Res Commun. 2018 Nov 17;506(1):102-107. doi: , 10.1016/j.bbrc.2018.10.067. Epub 2018 Oct 16. PMID:30336976[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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