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PXD015313 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMS analysis of cellular targets of an engineered selective PSD-95 PDZ domain ligand
DescriptionDesigning highly specific modulators of protein-protein interactions (PPIs) is especially challenging in the context of multiple paralogs and conserved interaction surfaces. In this case, direct generation of selective and competitive inhibitors is hindered by high similarity within the evolutionary-related protein interfaces and PPI domains. We report here a strategy that addresses this challenge by using a semi-rational approach that separates the modulator design into two functional parts. We first achieve specificity toward a region outside of the interface by employing a selection by phage display coupled with molecular and cellular validation. Highly selective competition is then generated by appending the more degenerate interaction peptide to bind against the target interface. We have applied this approach to PSD-95, an essential multi-PDZ domain-containing synaptic scaffold protein that belongs to a larger family of paralogs. We show here that with this strategy we could specifically target a single PDZ domain within the postsynaptic protein PSD-95 over highly similar PDZ domains in PSD-93, SAP-97 and SAP-102. Our work provides the first paralog-selective and domain specific inhibitor of PSD-95, and describes a method to efficiently target other conserved PPI modules. This archive contains the comparative LC/MS/MS analysis of cellular targets of an engineered selective PSD-95 PDZ domain ligand, Xph20-ETWV, against the fusion with a naïve clone, Xph0-ETWV and a control non-binding protein (mSacrlet-i).
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterClaverol Claverol
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-09-04 05:13:30ID requested
12019-11-11 18:18:12announced
Publication List
Rimbault C, Maruthi K, Breillat C, Genuer C, Crespillo S, Puente-Mu, ñ, oz V, Chamma I, Gauthereau I, Antoine S, Thibaut C, Tai FWJ, Dartigues B, Grillo-Bosch D, Claverol S, Poujol C, Choquet D, Mackereth CD, Sainlos M, Engineering selective competitors for the discrimination of highly conserved protein-protein interaction modules. Nat Commun, 10(1):4521(2019) [pubmed]
Keyword List
submitter keyword: Engineered ligand/PDZ domains/Pull-down
Contact List
Marc Bonneu
contact affiliationUniv. Bordeaux, Plateforme Proteome, 33000, Bordeaux, France ( lab head )
contact emailmarc.bonneu@ipb.fr
lab head
Claverol Claverol
contact affiliationPlateforme Proteome
contact emailstephane.claverol@u-bordeaux.fr
dataset submitter
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Dataset FTP location
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