title: Structural Basis of Eco1-Mediated Cohesin Acetylation.
abstract: 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.
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: William C H
authors.initials: WC
authors.lastname: Chao
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Benjamin O
authors.initials: BO
authors.lastname: Wade
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Céline
authors.initials: C
authors.lastname: Bouchoux
authors.affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Jones
authors.affiliation: Structural Biology Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Purkiss
authors.affiliation: Peptide Chemistry Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Stefania
authors.initials: S
authors.lastname: Federico
authors.affiliation: Peptide Chemistry Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: O'Reilly
authors.affiliation: Protein Analysis and Proteomics Platform, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Ambrosius P
authors.initials: AP
authors.lastname: Snijders
authors.affiliation: Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Uhlmann
authors.affiliation: Structural Biology of Chromosome Segregation Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Singleton
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D018360:Crystallography, X-Ray; D015870:Gene Expression; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D029867:Xenopus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; C427726:PDS5 protein, S cerevisiae; C476199:RAD61 protein, S cerevisiae; D011994:Recombinant Proteins; C120372:SMC3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D000098550:Structural Maintenance of Chromosome Protein 1; D000123:Acetyltransferases; C118076:ECO1 protein, S cerevisiae; C575500:Eco2 protein, Xenopus