Crystal structure of the Schizosaccharomyces pombe U7BR E2-binding region in complex with Ubc7
Year: 2019
Type: article
Abstract: Endoplasmic reticulum (ER)-associated degradation (ERAD) is a protein quality-control pathway in eukaryotes in which misfolded ER proteins are polyubiquitylated, extracted and ultimately degraded by the proteasome. This process involves ER membrane-embedded ubiquitin E2 and E3 enzymes, as well as a soluble E2 enzyme (Ubc7 in Saccharomyces cerevisiae and UBE2G2 in mammals). E2-binding regions (E2BRs) that recruit these soluble ERAD E2s to the ER have been identified in humans and S. cerevisiae, and structures of E2-E2BR complexes from both species have been determined. In addition to sequence and structural differences between the human and S. cerevisiae E2BRs, the binding of E2BRs also elicits different biochemical outcomes with respect to E2 charging by E1 and E2 discharge. Here, the Schizosaccharomyces pombe E2BR was identified and purified with Ubc7 to resolve a 1.7 Å resolution co-crystal structure of the E2BR in complex with Ubc7. The S. pombe E2BR binds to the back side of the E2 as an α-helix and, while differences exist, it exhibits greater similarity to the human E2BR. Structure-based sequence alignments reveal differences and conserved elements among these species. Structural comparisons and biochemistry reveal that the S. pombe E2BR presents a steric impediment to E1 binding and inhibits E1-mediated charging, respectively.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,800
Funders: Howard Hughes Medical Institute, U.S. Department of Energy, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory
Awards: G1313983767, G1461859851, G2164036156, G254657075, Structural studies of ubiquitin-like protein modification, Pixel Array Detector for X-ray Crystallography, G3407338877, G4102770861, G498139845, G5201631574, Structural and Functional Studies of Eukaryotic Exosomes, G666778509, NE-CAT Center for Advanced Macromolecular Crystallography, G9000003249, G9000119994, Cancer Center Support Grant, Structural studies of RNA processing and ubiquitin-like protein modification, G969889393
OpenAlex ID: W2965471056