A MUB E2 structure reveals E1 selectivity between cognate ubiquitin E2s in eukaryotes
| Autor: | Konstantin R. Malley, Brian P. Downes, Xiaolong Lu, Sergey Korolev, Olga Koroleva, Caitlin C. Brenner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Science Arabidopsis Protein Prenylation General Physics and Astronomy Crystallography X-Ray General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Ubiquitin Prenylation Protein Domains Amino Acid Sequence chemistry.chemical_classification Multidisciplinary biology Sequence Homology Amino Acid Arabidopsis Proteins Cell Membrane Ubiquitination Eukaryota Membrane Proteins General Chemistry biology.organism_classification Cell biology 030104 developmental biology Enzyme Biochemistry chemistry E2 protein Ubiquitin-Conjugating Enzymes biology.protein Selectivity Protein Binding |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-11 (2016) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Ubiquitin (Ub) is a protein modifier that controls processes ranging from protein degradation to endocytosis, but early-acting regulators of the three-enzyme ubiquitylation cascade are unknown. Here we report that the prenylated membrane-anchored ubiquitin-fold protein (MUB) is an early-acting regulator of subfamily-specific E2 activation. An AtMUB3:AtUBC8 co-crystal structure defines how MUBs inhibit E2∼Ub formation using a combination of E2 backside binding and a MUB-unique lap-bar loop to block E1 access. Since MUBs tether Arabidopsis group VI E2 enzymes (related to HsUbe2D and ScUbc4/5) to the plasma membrane, and inhibit E2 activation at physiological concentrations, they should function as potent plasma membrane localized regulators of Ub chain synthesis in eukaryotes. Our findings define a biochemical function for MUB, a family of highly conserved Ub-fold proteins, and provide an example of selective activation between cognate Ub E2s, previously thought to be constitutively activated by E1s. Regulators of the important ubiquitylation cascade are not well studied. Here, the authors report the crystal structure of a prenylated membrane-anchored ubiquitin-fold protein from Arabidopsis bound to an E2 protein and conclude that it is an example of selective activation between E2 enzymes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|