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Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein

The human Discs Large 1 (DLG1) protein uses two of its three PDZ domains to interact with the C-terminal peptide of the Adenomatous Polyposis Coli (APC) tumor suppressor protein. The DLG1/APC complex inhibits the cell cycle progression from the G0/G1 to the S phase, regulates epithelial cell migrati...

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Autores principales: Zhang, Zhenyi, Li, Hua, Chen, Leyi, Lu, Xingyu, Zhang, Jian, Xu, Ping, Lin, Kui, Wu, Geng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157396/
https://www.ncbi.nlm.nih.gov/pubmed/21858148
http://dx.doi.org/10.1371/journal.pone.0023507
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author Zhang, Zhenyi
Li, Hua
Chen, Leyi
Lu, Xingyu
Zhang, Jian
Xu, Ping
Lin, Kui
Wu, Geng
author_facet Zhang, Zhenyi
Li, Hua
Chen, Leyi
Lu, Xingyu
Zhang, Jian
Xu, Ping
Lin, Kui
Wu, Geng
author_sort Zhang, Zhenyi
collection PubMed
description The human Discs Large 1 (DLG1) protein uses two of its three PDZ domains to interact with the C-terminal peptide of the Adenomatous Polyposis Coli (APC) tumor suppressor protein. The DLG1/APC complex inhibits the cell cycle progression from the G0/G1 to the S phase, regulates epithelial cell migration and morphogenesis, and is required for polarization of the microtubule cytoskeleton. However, the molecular details of how DLG1 recognizes APC is not clear. In this study, we performed biochemical and biophysical assays to investigate the interactions between PDZ domains of DLG1 and the C-terminal peptide of APC. In addition, we determined the crystal structures of the PDZ1 and PDZ2 domains of DLG1 each in complex with the C-terminal 11-residue peptide of APC. Our biochemical, biophysical, and structural results revealed structural elements and residues on PDZ1 and PDZ2 domains of DLG1 and on APC crucial for their mutual interaction. In particular, our results show that the β2/β3 loops of PDZ1 and PDZ2 play important roles in contributing to the binding affinities between PDZ domains and APC, through interacting with the residues upstream of the canonical PDZ-binding S/T-X-V motif. The results provide new insights into the binding mode of a defined C-terminal segment of APC by the PDZ domains of DLG1.
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spelling pubmed-31573962011-08-19 Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein Zhang, Zhenyi Li, Hua Chen, Leyi Lu, Xingyu Zhang, Jian Xu, Ping Lin, Kui Wu, Geng PLoS One Research Article The human Discs Large 1 (DLG1) protein uses two of its three PDZ domains to interact with the C-terminal peptide of the Adenomatous Polyposis Coli (APC) tumor suppressor protein. The DLG1/APC complex inhibits the cell cycle progression from the G0/G1 to the S phase, regulates epithelial cell migration and morphogenesis, and is required for polarization of the microtubule cytoskeleton. However, the molecular details of how DLG1 recognizes APC is not clear. In this study, we performed biochemical and biophysical assays to investigate the interactions between PDZ domains of DLG1 and the C-terminal peptide of APC. In addition, we determined the crystal structures of the PDZ1 and PDZ2 domains of DLG1 each in complex with the C-terminal 11-residue peptide of APC. Our biochemical, biophysical, and structural results revealed structural elements and residues on PDZ1 and PDZ2 domains of DLG1 and on APC crucial for their mutual interaction. In particular, our results show that the β2/β3 loops of PDZ1 and PDZ2 play important roles in contributing to the binding affinities between PDZ domains and APC, through interacting with the residues upstream of the canonical PDZ-binding S/T-X-V motif. The results provide new insights into the binding mode of a defined C-terminal segment of APC by the PDZ domains of DLG1. Public Library of Science 2011-08-17 /pmc/articles/PMC3157396/ /pubmed/21858148 http://dx.doi.org/10.1371/journal.pone.0023507 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Zhang, Zhenyi
Li, Hua
Chen, Leyi
Lu, Xingyu
Zhang, Jian
Xu, Ping
Lin, Kui
Wu, Geng
Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title_full Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title_fullStr Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title_full_unstemmed Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title_short Molecular Basis for the Recognition of Adenomatous Polyposis Coli by the Discs Large 1 Protein
title_sort molecular basis for the recognition of adenomatous polyposis coli by the discs large 1 protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157396/
https://www.ncbi.nlm.nih.gov/pubmed/21858148
http://dx.doi.org/10.1371/journal.pone.0023507
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