PXD025300

PXD025300 is an original dataset announced via ProteomeXchange.

Title	Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry
Description	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.
HostingRepository	PRIDE
AnnounceDate	2021-06-07
AnnouncementXML	Submission_2021-06-07_02:48:33.600.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Brenda Rosa
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-09 03:54:51	ID requested
⏵ 1	2021-06-07 02:48:34	announced

Rosa B, Dickinson ER, Marchetti M, Campanini B, Pioselli B, Bettati S, Rand KD, Revealing the Dynamic Allosteric Changes Required for Formation of the Cysteine Synthase Complex by Hydrogen-Deuterium Exchange MS. Mol Cell Proteomics, 20():100098(2021) [pubmed]

submitter keyword: Cysteine biosynthesis, bienzyme complex, protein-protein interactions, allosteric regulation, cysteine synthase, E. coli, Synapt G2-Si, Hydrogen deuterium exchange (hdx-ms)

Kasper Dyrberg Rand
contact affiliation	Protein Analysis Group, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen O, Denmark
contact email	kasper.rand@sund.ku.dk
lab head
Brenda Rosa
contact affiliation	University of Parma
contact email	brenda.rosa@studenti.unipr.it
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025300
     1. Label: PRIDE project
     2. Name: Revealing the dynamic allosteric changes required for formation of the cysteine synthase complex by hydrogen-deuterium exchange mass spectrometry