Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry
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Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry. / Rosa, Brenda; Dickinson, Eleanor R; Marchetti, Marialaura; Campanini, Barbara; Pioselli, Barbara; Bettati, Stefano; Rand, Kasper Dyrberg.
In: Molecular and Cellular Proteomics, Vol. 20, 100098, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry
AU - Rosa, Brenda
AU - Dickinson, Eleanor R
AU - Marchetti, Marialaura
AU - Campanini, Barbara
AU - Pioselli, Barbara
AU - Bettati, Stefano
AU - Rand, Kasper Dyrberg
N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2021
Y1 - 2021
N2 - CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase (CS), with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange mass spectrometry to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intra-trimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a longer-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a non-random orientation. These results provide new molecular insights into the allosteric formation of the CS complex and could help guide antibacterial drug design.
AB - CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase (CS), with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange mass spectrometry to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intra-trimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a longer-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a non-random orientation. These results provide new molecular insights into the allosteric formation of the CS complex and could help guide antibacterial drug design.
U2 - 10.1016/j.mcpro.2021.100098
DO - 10.1016/j.mcpro.2021.100098
M3 - Journal article
C2 - 34022432
VL - 20
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
SN - 1535-9476
M1 - 100098
ER -
ID: 271541705