Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis
Kouznetsova, Ekaterina ; Kanno, Takaharu ; Karlberg, Tobias LU ; Thorsell, Ann-Gerd ; Wisniewska, Magdalena ; Kursula, Petri ; Sjögren, Camilla and Schüler, Herwig LU
(2016)
In Structure
24(5).
p.789-796
- Abstract
Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at... (More)
Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at the conserved residue D114, adjacent to the cohesion-activating acetylation site K112,K113, cannot be acetylated in vivo. This indicates that ESCO1 controls cohesion through substrate-assisted catalysis. Thus, this study discloses a key mechanism for cohesion establishment.
(Less)
- author
- Kouznetsova, Ekaterina
; Kanno, Takaharu
; Karlberg, Tobias
LU
; Thorsell, Ann-Gerd
; Wisniewska, Magdalena
; Kursula, Petri
; Sjögren, Camilla
and Schüler, Herwig
LU
- publishing date
- 2016-05-03
- type
- Contribution to journal
- publication status
- published
- keywords
- Acetyl Coenzyme A/metabolism, Acetyltransferases/chemistry, Catalytic Domain, Cell Cycle Proteins/chemistry, Chromosomal Proteins, Non-Histone/chemistry, Crystallography, X-Ray, Humans, Molecular Docking Simulation, Mutation, Protein Binding, Protein Multimerization, Saccharomyces cerevisiae/enzymology, Saccharomyces cerevisiae Proteins/chemistry
- in
- Structure
- volume
- 24
- issue
- 5
- pages
- 8 pages
- publisher
- Cell Press
- external identifiers
-
- scopus:84963945525
- pmid:27112597
- ISSN
- 0969-2126
- DOI
- 10.1016/j.str.2016.03.021
- language
- English
- LU publication?
- no
- additional info
- Copyright © 2016 Elsevier Ltd. All rights reserved.
- id
- c4772aeb-5b6f-4d50-8adc-2a2c88f41a4b
- date added to LUP
- 2024-11-21 17:52:06
- date last changed
- 2025-01-03 07:41:44
@article{c4772aeb-5b6f-4d50-8adc-2a2c88f41a4b,
abstract = {{<p>Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at the conserved residue D114, adjacent to the cohesion-activating acetylation site K112,K113, cannot be acetylated in vivo. This indicates that ESCO1 controls cohesion through substrate-assisted catalysis. Thus, this study discloses a key mechanism for cohesion establishment.</p>}},
author = {{Kouznetsova, Ekaterina and Kanno, Takaharu and Karlberg, Tobias and Thorsell, Ann-Gerd and Wisniewska, Magdalena and Kursula, Petri and Sjögren, Camilla and Schüler, Herwig}},
issn = {{0969-2126}},
keywords = {{Acetyl Coenzyme A/metabolism; Acetyltransferases/chemistry; Catalytic Domain; Cell Cycle Proteins/chemistry; Chromosomal Proteins, Non-Histone/chemistry; Crystallography, X-Ray; Humans; Molecular Docking Simulation; Mutation; Protein Binding; Protein Multimerization; Saccharomyces cerevisiae/enzymology; Saccharomyces cerevisiae Proteins/chemistry}},
language = {{eng}},
month = {{05}},
number = {{5}},
pages = {{789--796}},
publisher = {{Cell Press}},
series = {{Structure}},
title = {{Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis}},
url = {{http://dx.doi.org/10.1016/j.str.2016.03.021}},
doi = {{10.1016/j.str.2016.03.021}},
volume = {{24}},
year = {{2016}},
}