⮝ Full datasets listing

PXD033055

PXD033055 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe molecular bases of spinal muscular atrophy
DescriptionSpinal muscular atrophy (SMA) is a neurodegenerative disease caused by the absence of a functional Survival of Motor Neuron 1 gene (SMN1). The nearly identical paralog, SMN2, cannot compensate for the loss of SMN1 because exon 7 is aberrantly skipped from most SMN2 transcripts, a process mediated by synergistic activities of Sam68/KHDR1 and hnRNP A1. This results in the production of a truncated, non-functional protein that is rapidly degraded. Here we present several crystal structures of Sam68 RNA-binding domain (RBD). Sam68-RBD forms stable symmetric homodimers by antiparallel association of helices α3 from two monomers. However, the details of domain organization and the dimerization interface differ significantly from previously characterized homologs. We demonstrate that Sam68 and hnRNP A1 bind proximal but distinct motifs within the central region of SMN2(ex7). Our findings have important implications for the etiology of SMA and open new avenues for the design of novel therapeutics to treat splicing diseases.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:41:32.489.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD033055
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMarta Vilaseca
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-04-07 03:11:18ID requested
12024-05-22 23:42:23announced
22024-10-22 06:41:35announced2024-10-22: Updated project metadata.
Publication List
Nadal M, Anton R, Dorca-Ar, é, valo J, Est, é, banez-Perpi, ñ, á E, Tizzano EF, Fuentes-Prior P, Structure and function analysis of Sam68 and hnRNP A1 synergy in the exclusion of exon 7 from SMN2 transcripts. Protein Sci, 32(4):e4553(2023) [pubmed]
10.6019/PXD033055;
10.1002/pro.4553;
Keyword List
submitter keyword: Biological sciences/Molecular biology/RNA metabolism/Alternative splicing Biological sciences/Structural biology/X-ray crystallography Health sciences/Diseases/Neurological disorders/Motor neuron disease
Contact List
Mireia Diaz
contact affiliationMass Spectometry and Protemics Core Facility, Institute for Research in Biomedicine
contact emailmireia.diaz@irbbarcelona.org
lab head
Marta Vilaseca
contact affiliationMass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact emailmasspe@irbbarcelona.org
dataset submitter
Full Dataset Link List
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/2024/05/PXD033055
PRIDE project URI
Repository Record List
[ + ]