PXD018172

PXD018172 is an original dataset announced via ProteomeXchange.

Title	Structural basis for DNA recognition and allosteric control of the Retinoic Acid Receptors RAR-RXR
Description	Retinoic Acid Receptors (RARs) as a functional heterodimer with Retinoid X Receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insight for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structure of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, on DR0 the two molecules bound non-cooperatively on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding mode between DR0 and DR5 were observed leading to differences in the conformation and structural dynamics of the multi-domain RXR-RAR DNA complex. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:18:47.356.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maxime BOURGUET
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-24 23:15:54	ID requested
1	2021-02-10 09:17:06	announced
2	2021-02-10 23:09:39	announced	2021-02-11: Updated project metadata.
⏵ 3	2024-10-22 05:18:48	announced	2024-10-22: Updated project metadata.

10.1093/nar/gkaa697;

Osz J, McEwen AG, Bourguet M, Przybilla F, Peluso-Iltis C, Poussin-Courmontagne P, M, é, ly Y, Cianf, é, rani S, Jeffries CM, Svergun DI, Rochel N, Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR-RXR. Nucleic Acids Res, 48(17):9969-9985(2020) [pubmed]

submitter keyword: HDX,Nuclear receptors, structural MS, HDX-MS

Sarah Cianférani
contact affiliation	IPHC (LSMBO - Laboratoire de Spectrométrie de Masse Bio-Organique), UMR 7178, Université de Strasbourg, CNRS
contact email	sarah.cianferani@unistra.fr
lab head
Maxime BOURGUET
contact affiliation	LSMBO - IPHC / CNRS
contact email	maxime.bourguet@etu.unistra.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/02/PXD018172

PRIDE project URI

• PRIDE
  1. PXD018172
     1. Label: PRIDE project
     2. Name: Structural basis for DNA recognition and allosteric control of the Retinoic Acid Receptors RAR-RXR