Dataset Information

Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.

ABSTRACT: Syntenin has crucial roles in cell adhesion, cell migration and synaptic transmission. Its closely linked postsynaptic density-95, discs large 1, zonula occludens-1 (PDZ) domains typically interact with C-terminal ligands. We profile syntenin PDZ1-2 through proteomic peptide phage display (ProP-PD) using a library that displays C-terminal regions of the human proteome. The protein recognizes a broad range of peptides, with a preference for hydrophobic motifs and has a tendency to recognize cryptic internal ligands. We validate the interaction with nectin-1 through orthogonal assays. The study demonstrates the power of ProP-PD as a complementary approach to uncover interactions of potential biological relevance.

SUBMITTER: Garrido-Urbani S

PROVIDER: S-EPMC4819696 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.

Garrido-Urbani Sarah S Garg Pankaj P Ghossoub Rania R Arnold Roland R Lembo Frédérique F Sundell Gustav N GN Kim Philip M PM Lopez Marc M Zimmermann Pascale P Sidhu Sachdev S SS Ivarsson Ylva Y

FEBS letters 20160108 1

Syntenin has crucial roles in cell adhesion, cell migration and synaptic transmission. Its closely linked postsynaptic density-95, discs large 1, zonula occludens-1 (PDZ) domains typically interact with C-terminal ligands. We profile syntenin PDZ1-2 through proteomic peptide phage display (ProP-PD) using a library that displays C-terminal regions of the human proteome. The protein recognizes a broad range of peptides, with a preference for hydrophobic motifs and has a tendency to recognize crypt ...[more]

PMID: 26787460

Similar Datasets

Project description:PurposeHER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment. PET imaging of HER3 expression may permit a more personalized approach to targeted therapy by allowing for detection of HER3-mediated resistance, in addition to informing clinical trial patient selection for novel therapies targeting HER3.ProceduresPhage display selection targeting the HER3 extracellular domain was performed in order to develop a peptide with optimal blood clearance and highly accurate HER3 quantification.ResultsThe selection converged to a consensus peptide sequence that was subsequently found to bind HER3 with an affinity of 270 ± 151 nM. The peptide, termed HER3P1, was bound with high selectivity to HER3 over other similar receptor tyrosine kinases such as EGFR and HER2. Furthermore, HER3P1 was able to distinguish between high and low HER3-expressing cells in vitro. The peptide was radiolabeled with Ga-68 and demonstrated to specifically bind HER3 by in vivo PET imaging. Uptake of [68Ga]HER3P1 was highly specific for HER3-positive tumors, with tumor-to-background ratios ranging from 1.59-3.32, compared to those of HER3-negative tumors, ranging from 0.84-0.93. The uptake of [68Ga]HER3P1 also demonstrated high (P < 0.001) correlation with protein expression as quantified by Western blot and confirmed by biodistribution.ConclusionsHER3P1 accurately quantifies expression of HER3 by PET imaging and has potential utility as a clinical imaging agent.

Dataset Information

Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.

Publications

Proteomic peptide phage display uncovers novel interactions of the PDZ1-2 supramodule of syntenin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets