PXD033055 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The molecular bases of spinal muscular atrophy |
Description | Spinal 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. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:41:32.489.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD033055 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Marta Vilaseca |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-04-07 03:11:18 | ID requested | |
1 | 2024-05-22 23:42:23 | announced | |
⏵ 2 | 2024-10-22 06:41:35 | announced | 2024-10-22: 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 affiliation | Mass Spectometry and Protemics Core Facility, Institute for Research in Biomedicine |
contact email | mireia.diaz@irbbarcelona.org |
lab head | |
Marta Vilaseca |
contact affiliation | Mass 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 email | masspe@irbbarcelona.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD033055
- Label: PRIDE project
- Name: The molecular bases of spinal muscular atrophy