5KNL

Crystal structure of S. pombe ubiquitin E1 (Uba1) in complex with Ubc15 and ubiquitin

Summary for 5KNL

• Entry DOI: 10.2210/pdb5knl/pdb
• Descriptor: Ubiquitin-activating enzyme E1 1, Ubiquitin, Ubiquitin-conjugating enzyme E2 15, ... (5 entities in total)
• Functional Keywords: ubiquitin, e1, e2, uba1, ubc15, conformational change, thioester, adenylation, thioester transfer (transthioesterification), atp-binding, ubiquitin e2 binding, ubiquitination, ligase
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 6
• Total formula weight: 286600.94

Authors

Olsen, S.K.,Lv, Z.,Yuan, L.,Williams, K. (deposition date: 2016-06-28, release date: 2017-02-15, Last modification date: 2024-11-06)

Primary citation

Lv, Z.,Rickman, K.A.,Yuan, L.,Williams, K.,Selvam, S.P.,Woosley, A.N.,Howe, P.H.,Ogretmen, B.,Smogorzewska, A.,Olsen, S.K.
S. pombe Uba1-Ubc15 Structure Reveals a Novel Regulatory Mechanism of Ubiquitin E2 Activity.
Mol. Cell, 65:699-714.e6, 2017

PubMed Abstract: Ubiquitin (Ub) E1 initiates the Ub conjugation cascade by activating and transferring Ub to tens of different E2s. How Ub E1 cooperates with E2s that differ substantially in their predicted E1-interacting residues is unknown. Here, we report the structure of S. pombe Uba1 in complex with Ubc15, a Ub E2 with intrinsically low E1-E2 Ub thioester transfer activity. The structure reveals a distinct Ubc15 binding mode that substantially alters the network of interactions at the E1-E2 interface compared to the only other available Ub E1-E2 structure. Structure-function analysis reveals that the intrinsically low activity of Ubc15 largely results from the presence of an acidic residue at its N-terminal region. Notably, Ub E2 N termini are serine/threonine rich in many other Ub E2s, leading us to hypothesize that phosphorylation of these sites may serve as a novel negative regulatory mechanism of Ub E2 activity, which we demonstrate biochemically and in cell-based assays.

PubMed: 28162934
DOI: 10.1016/j.molcel.2017.01.008

Experimental method

X-RAY DIFFRACTION (2.5 Å)