Structural basis of Eco1-mediated cohesin acetylation
journal contributionposted on 05.08.2020, 17:08 by William CH Chao, Benjamin O Wade, Céline Bouchoux, Andrew W Jones, Andrew G Purkiss, Stefania Federico, Nicola O'Reilly, Ambrosius P Snijders, Frank Uhlmann, Martin R Singleton
Sister-chromatid cohesion is established by Eco1-mediated acetylation on two conserved tandem lysines in the cohesin Smc3 subunit. However, the molecular basis of Eco1 substrate recognition and acetylation in cohesion is not fully understood. Here, we discover and rationalize the substrate specificity of Eco1 using mass spectrometry coupled with in-vitro acetylation assays and crystallography. Our structures of the X. laevis Eco2 (xEco2) bound to its primary and secondary Smc3 substrates demonstrate the plasticity of the substrate-binding site, which confers substrate specificity by concerted conformational changes of the central β hairpin and the C-terminal extension.
AcetylationAcetyltransferasesAmino Acid SequenceAnimalsBinding SitesCell Cycle ProteinsChromosomal Proteins, Non-HistoneChromosome SegregationCrystallography, X-RayGene ExpressionModels, MolecularNuclear ProteinsProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSequence Homology, Amino AcidSubstrate SpecificityXenopus ProteinsXenopus laevisUhlmann FC001198Singleton FC001155PCSBPRT0601 Biochemistry and Cell Biology0299 Other Physical Sciences