4r62

Structure of Rad6~Ub

spinqualitylabelsall models 4r62, resolution 2.28Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4r62 is a 2 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.28Å Ligands: ACT Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UBC2_YEAST Catalyzes the covalent attachment of ubiquitin to other proteins. In association with the E3 enzyme BRE1 and LGE1, it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B to form H2BK123ub1. H2BK123ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In association with the E3 enzyme RAD18, it catalyzes the monoubiquitination of POL30 'Lys-164', involved in postreplication repair of UV-damaged DNA. The RAD6/UBC2-RAD18 complex is also involved in prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine. In association with the E3 enzyme UBR1, is involved in N-end rule-dependent protein degradation. Also involved in sporulation. Publication Abstract from PubMed Rad6 is a yeast E2 ubiquitin conjugating enzyme that monoubiquitinates histone H2B in conjunction with the E3, Bre1, but can non-specifically modify histones on its own. We determined the crystal structure of a Rad6 approximately Ub thioester mimic, which revealed a network of interactions in the crystal in which the ubiquitin in one conjugate contacts Rad6 in another. The region of Rad6 contacted is located on the distal face of Rad6 opposite the active site, but differs from the canonical E2 backside that mediates free ubiquitin binding and polyubiquitination activity in other E2 enzymes. We find that free ubiquitin interacts weakly with both non-canonical and canonical backside residues of Rad6 and that mutations of non-canonical residues have deleterious effects on Rad6 activity comparable to those observed to mutations in the canonical E2 backside. The effect of non-canonical backside mutations is similar in the presence and absence of Bre1, indicating that contacts with non-canonical backside residues govern the intrinsic activity of Rad6. Our findings shed light on the determinants of intrinsic Rad6 activity and reveal new ways in which contacts with an E2 backside can regulate ubiquitin conjugating activity. Role of a non-canonical surface of Rad6 in ubiquitin conjugating activity.,Kumar P, Magala P, Geiger-Schuller KR, Majumdar A, Tolman JR, Wolberger C Nucleic Acids Res. 2015 Aug 18. pii: gkv845. PMID:26286193 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 3D structures of ubiquitin conjugating enzyme

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