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Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain

FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their μ homology domains (μHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity μHD-binding site in Eps15 is a r...

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Autores principales: Shimada, Atsushi, Yamaguchi, Atsuko, Kohda, Daisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731787/
https://www.ncbi.nlm.nih.gov/pubmed/26822536
http://dx.doi.org/10.1038/srep19565
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author Shimada, Atsushi
Yamaguchi, Atsuko
Kohda, Daisuke
author_facet Shimada, Atsushi
Yamaguchi, Atsuko
Kohda, Daisuke
author_sort Shimada, Atsushi
collection PubMed
description FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their μ homology domains (μHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity μHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal μHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 μHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the μHD, which is distinct from those of other distantly related μHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the μHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in μHD binding.
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spelling pubmed-47317872016-02-04 Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain Shimada, Atsushi Yamaguchi, Atsuko Kohda, Daisuke Sci Rep Article FCHo1, FCHo2, and SGIP1 are key regulators of clathrin-mediated endocytosis. Their μ homology domains (μHDs) interact with the C-terminal region of an endocytic scaffold protein, Eps15, containing fifteen Asp-Pro-Phe (DPF) motifs. Here, we show that the high-affinity μHD-binding site in Eps15 is a region encompassing six consecutive DPF motifs, while the minimal μHD-binding unit is two consecutive DPF motifs. We present the crystal structures of the SGIP1 μHD in complex with peptides containing two DPF motifs. The peptides bind to a novel ligand-binding site of the μHD, which is distinct from those of other distantly related μHD-containing proteins. The two DPF motifs, which adopt three-dimensional structures stabilized by sequence-specific intramotif and intermotif interactions, are extensively recognized by the μHD and are both required for binding. Thus, consecutive and singly scattered DPF motifs play distinct roles in μHD binding. Nature Publishing Group 2016-01-29 /pmc/articles/PMC4731787/ /pubmed/26822536 http://dx.doi.org/10.1038/srep19565 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Shimada, Atsushi
Yamaguchi, Atsuko
Kohda, Daisuke
Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title_full Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title_fullStr Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title_full_unstemmed Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title_short Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain
title_sort structural basis for the recognition of two consecutive mutually interacting dpf motifs by the sgip1 μ homology domain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4731787/
https://www.ncbi.nlm.nih.gov/pubmed/26822536
http://dx.doi.org/10.1038/srep19565
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