4gba
From Proteopedia
DCNL complex with N-terminally acetylated NEDD8 E2 peptide
Structural highlights
FunctionDCNL3_HUMAN Potently stimulates the neddylation of cullin components of SCF-type E3 ubiquitin ligase complexes from the NEDD8-conjugating E2 enzyme UBE2F. Neddylation of cullins play an essential role in the regulation of SCF-type complexes activity.[1] Publication Abstract from PubMedLittle is known about molecular recognition of acetylated N termini, despite prevalence of this modification among eukaryotic cytosolic proteins. We report that the family of human DCN-like (DCNL) co-E3s, which promote ligation of the ubiquitin-like protein NEDD8 to cullin targets, recognizes acetylated N termini of the E2 enzymes UBC12 and UBE2F. Systematic biochemical and biophysical analyses reveal 40- and 10-fold variations in affinities among different DCNL-cullin and DCNL-E2 complexes, contributing to varying efficiencies of different NEDD8 ligation cascades. Structures of DCNL2 and DCNL3 complexes with N-terminally acetylated peptides from UBC12 and UBE2F illuminate a common mechanism by which DCNL proteins recognize N-terminally acetylated E2s and how selectivity for interactions dependent on N-acetyl-methionine are established through side chains recognizing distal residues. Distinct preferences of UBC12 and UBE2F peptides for inhibiting different DCNLs, including the oncogenic DCNL1 protein, suggest it may be possible to develop small molecules blocking specific N-acetyl-methionine-dependent protein interactions. Structural Conservation of Distinctive N-terminal Acetylation-Dependent Interactions across a Family of Mammalian NEDD8 Ligation Enzymes.,Monda JK, Scott DC, Miller DJ, Lydeard J, King D, Harper JW, Bennett EJ, Schulman BA Structure. 2012 Nov 27. pii: S0969-2126(12)00409-1. doi:, 10.1016/j.str.2012.10.013. PMID:23201271[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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