Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/61106
Title: Affinity enhancement by ligand clustering effect inspired by peptide dendrimers-shank PDZ proteins interactions
Authors: Liu, J
Liu, M
Zheng, B 
Yao, Z 
Xia, J
Issue Date: 2016
Publisher: Public Library of Science
Source: PLoS one, 2016, v. 11, no. 2, e0149580 How to cite?
Journal: PLoS one 
Abstract: High-affinity binders are desirable tools to probe the function that specific protein-protein interactions play in cell. In the process of seeking a general strategy to design high-affinity binders, we found a clue from the βPIX (p21-activated kinase interacting exchange factor) -Shank PDZ interaction in synaptic assembly: three PDZ-binding sites are clustered by a parallel coiled-coil trimer but bind to Shank PDZ protein with 1:1 stoichiometry (1 trimer/1 PDZ). Inspired by this architecture, we proposed that peptide dendrimer, mimicking the ligand clustering in βPIX, will also show enhanced binding affinity, yet with 1:1 stoichiometry. This postulation has been proven here, as we synthesized a set of monomeric, dimeric and trimeric peptides and measured their binding affinity and stoichiometry with Shank PDZ domains by isothermal titration calorimetry, native mass spectrometry and surface plasmon resonance. This affinity enhancement, best explained by proximity effect, will be useful to guide the design of high-affinity blockers for protein-protein interactions.
URI: http://hdl.handle.net/10397/61106
EISSN: 1932-6203
DOI: 10.1371/journal.pone.0149580
Rights: © 2016 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The following publication: Liu J, Liu M, Zheng B, Yao Z, Xia J (2016) Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers−Shank PDZ Proteins Interactions. PLoS ONE 11(2): e0149580 is available at https://doi.org/10.1371/journal.pone.0149580
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