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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4731787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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