PXD047111

PXD047111 is an original dataset announced via ProteomeXchange.

Title	Interaction proteomics of WT and disease variants of the human Creatine Transporter (SLC6A8)
Description	Creatine is an essential metabolite for the storage and rapid supply of energy in muscle and nerve cells. In humans, the creatine deficiency syndrome (CDS) is manifested by impaired metabolism, transport, and distribution of creatine throughout the body leading to severe forms of mental disabilities. One of the common cause of CDS is mutations that impact the function of the creatine transporter (SLC6A8). This study characterized 30 missense variants of SLC6A8, which include 15 variants of unknown significance and two which were not reported before. These variants were expressed in HEK293 cells, and their subcellular localization and transport activity was assessed. Further, for the first time the interactome of SLC6A8 WT was characterized by quantitative interaction proteomics. Computational methods were then used to first assess the impact of mutations upon the thermodynamic stability of SLC6A8. This was expanded by modeling the impact of mutations upon the inward and outward facing transporter conformation. Next, identified SLC6A8 protein interactions binary complexes were modelled and used to characterize the impact of variants upon the thermodynamic stability of the complexes. This was followed up, by performing for a subset of the variants the interaction proteomics analysis to study changes upon the identified SLC6A8 WT interactome.
HostingRepository	PRIDE
AnnounceDate	2024-01-04
AnnouncementXML	Submission_2024-01-04_06:09:47.300.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Frommelt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-20 12:50:46	ID requested
⏵ 1	2024-01-04 06:09:48	announced

Ferrada E, Wiedmer T, Wang WA, Frommelt F, Steurer B, Klimek C, Lindinger S, Osthushenrich T, Garofoli A, Brocchetti S, Bradberry S, Huang J, MacNamara A, Scarabottolo L, Ecker GF, Malarstig A, Superti-Furga G, Experimental and Computational Analysis of Newly Identified Pathogenic Mutations in the Creatine Transporter SLC6A8. J Mol Biol, 436(2):168383(2024) [pubmed]

10.1016/j.jmb.2023.168383;

submitter keyword: AP-MS,SLC6A8, Protein interactions, pathogenic variants

Giulio Superti-Furga
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
contact email	gsuperti@cemm.oeaw.ac.at
lab head
Fabian Frommelt
contact affiliation	CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
contact email	fabian.frommelt@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047111
     1. Label: PRIDE project
     2. Name: Interaction proteomics of WT and disease variants of the human Creatine Transporter (SLC6A8)