PXD015366

PXD015366 is an original dataset announced via ProteomeXchange.

Title	MS analysis of photocrosslink adducts for the mapping of interaction sites of selective engineered PSD-95 PDZ domain ligands
Description	Designing 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.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-11_18:38:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephane Claverol
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-09 03:24:05	ID requested
⏵ 1	2019-11-11 18:38:45	announced

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]

submitter keyword: Engineered ligand/PDZ domains/photocrosslinking/p-azidophenylalanine

Marc Bonneu
contact affiliation	Univ. Bordeaux, Plateforme Proteome, 33000, Bordeaux, France
contact email	marc.bonneu@ipb.fr
lab head
Stephane Claverol
contact affiliation	Plateforme Proteome
contact email	stephane.claverol@u-bordeaux.fr
dataset submitter

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/2019/11/PXD015366

PRIDE project URI

• PRIDE
  1. PXD015366
     1. Label: PRIDE project
     2. Name: MS analysis of photocrosslink adducts for the mapping of interaction sites of selective engineered PSD-95 PDZ domain ligands