PXD005575

PXD005575 is an original dataset announced via ProteomeXchange.

Title	Structure of the Homodimeric Androgen Receptor Ligand-Binding Domain
Description	The androgen receptor (AR) plays a crucial role in normal physiology, development and metabolism as well as in the etiology and treatment of diverse pathologies such as androgen insensitivity syndromes (AIS), male infertility, and prostate cancer (PCa). Here, we show that dimerization of AR ligand-binding domain (LBD) is induced by receptor agonists but not by antagonists. The 2.15-Å crystal structure of homodimeric, agonist- and coactivator peptide bound AR-LBD unveils a 1,000-Å2 large dimerization surface, which harbors over 40 previously unexplained AIS- and PCa-associated point mutations. An AIS mutation in the self-association interface (P767A) disrupts dimer formation in vivo, and has a detrimental effect on the transactivating properties of full-length AR, despite retained hormone-binding capacity. The conservation of essential residues suggests that the newly unveiled dimerization mechanism might be shared by other nuclear receptors. Our work defines AR-LBD homodimerization as an essential step in the proper functioning of this important transcription factor.
HostingRepository	PRIDE
AnnounceDate	2018-10-26
AnnouncementXML	Submission_2018-10-26_11:22:50.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marta Vilaseca
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	LTQ FT

Revision	Datetime	Status	ChangeLog Entry
0	2016-12-15 07:14:28	ID requested
⏵ 1	2018-10-26 11:22:51	announced

Nadal M, Prekovic S, Gallastegui N, Helsen C, Abella M, Zielinska K, Gay M, Vilaseca M, Taul, è, s M, Houtsmuller AB, van Royen ME, Claessens F, Fuentes-Prior P, Est, é, banez-Perpi, ñ, á E, Structure of the homodimeric androgen receptor ligand-binding domain. Nat Commun, 8():14388(2017) [pubmed]

curator keyword: Biological

submitter keyword: Cross-linking, AR

Marta Vilaseca Casas
contact affiliation	Mass Spectrometry and Proteomics Core Facility, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
contact email	marta.vilaseca@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliation	Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain
contact email	marta.vilaseca@irbbarcelona.org
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/2018/10/PXD005575

PRIDE project URI

• PRIDE
  1. PXD005575
     1. Label: PRIDE project
     2. Name: Structure of the Homodimeric Androgen Receptor Ligand-Binding Domain