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PXD015366 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMS analysis of photocrosslink adducts for the mapping of interaction sites of selective engineered PSD-95 PDZ domain ligands
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 mapping by photocrosslinking and LC/MS/MS analysis of the interaction sites of engineered selective PSD-95 PDZ domain ligands, Xph20-ETWV, Xph20-Stg and Xph20-ETMA.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterStephane Claverol
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-09-09 03:24:05ID requested
12019-11-11 18:38:45announced
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/photocrosslinking/p-azidophenylalanine
Contact List
Marc Bonneu
contact affiliationUniv. Bordeaux, Plateforme Proteome, 33000, Bordeaux, France
contact emailmarc.bonneu@ipb.fr
lab head
Stephane Claverol
contact affiliationPlateforme Proteome
contact emailstephane.claverol@u-bordeaux.fr
dataset submitter
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Dataset FTP location
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