Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions.
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 interactio...
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doaj-8683439a4d7649da84d9e26b586d9f662020-11-24T21:09:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014958010.1371/journal.pone.0149580Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions.Jiahui LiuMiao LiuBo ZhengZhongping YaoJiang XiaHigh-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.http://europepmc.org/articles/PMC4769301?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jiahui Liu Miao Liu Bo Zheng Zhongping Yao Jiang Xia |
spellingShingle |
Jiahui Liu Miao Liu Bo Zheng Zhongping Yao Jiang Xia Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. PLoS ONE |
author_facet |
Jiahui Liu Miao Liu Bo Zheng Zhongping Yao Jiang Xia |
author_sort |
Jiahui Liu |
title |
Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. |
title_short |
Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. |
title_full |
Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. |
title_fullStr |
Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. |
title_full_unstemmed |
Affinity Enhancement by Ligand Clustering Effect Inspired by Peptide Dendrimers-Shank PDZ Proteins Interactions. |
title_sort |
affinity enhancement by ligand clustering effect inspired by peptide dendrimers-shank pdz proteins interactions. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2016-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4769301?pdf=render |
work_keys_str_mv |
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