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Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities
Phox homology (PX) domains are membrane interacting domains that bind to phosphatidylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid PtdIns3P, others interact with alternative phos...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449406/ https://www.ncbi.nlm.nih.gov/pubmed/30948714 http://dx.doi.org/10.1038/s41467-019-09355-y |
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author | Chandra, Mintu Chin, Yanni K.-Y. Mas, Caroline Feathers, J. Ryan Paul, Blessy Datta, Sanchari Chen, Kai-En Jia, Xinying Yang, Zhe Norwood, Suzanne J. Mohanty, Biswaranjan Bugarcic, Andrea Teasdale, Rohan D. Henne, W. Mike Mobli, Mehdi Collins, Brett M. |
author_facet | Chandra, Mintu Chin, Yanni K.-Y. Mas, Caroline Feathers, J. Ryan Paul, Blessy Datta, Sanchari Chen, Kai-En Jia, Xinying Yang, Zhe Norwood, Suzanne J. Mohanty, Biswaranjan Bugarcic, Andrea Teasdale, Rohan D. Henne, W. Mike Mobli, Mehdi Collins, Brett M. |
author_sort | Chandra, Mintu |
collection | PubMed |
description | Phox homology (PX) domains are membrane interacting domains that bind to phosphatidylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid PtdIns3P, others interact with alternative phosphoinositides, and a precise understanding of how these specificities arise has remained elusive. Here we systematically screen all human PX domains for their phospholipid preferences using liposome binding assays, biolayer interferometry and isothermal titration calorimetry. These analyses define four distinct classes of human PX domains that either bind specifically to PtdIns3P, non-specifically to various di- and tri-phosphorylated phosphoinositides, bind both PtdIns3P and other phosphoinositides, or associate with none of the lipids tested. A comprehensive evaluation of PX domain structures reveals two distinct binding sites that explain these specificities, providing a basis for defining and predicting the functional membrane interactions of the entire PX domain protein family. |
format | Online Article Text |
id | pubmed-6449406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64494062019-04-08 Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities Chandra, Mintu Chin, Yanni K.-Y. Mas, Caroline Feathers, J. Ryan Paul, Blessy Datta, Sanchari Chen, Kai-En Jia, Xinying Yang, Zhe Norwood, Suzanne J. Mohanty, Biswaranjan Bugarcic, Andrea Teasdale, Rohan D. Henne, W. Mike Mobli, Mehdi Collins, Brett M. Nat Commun Article Phox homology (PX) domains are membrane interacting domains that bind to phosphatidylinositol phospholipids or phosphoinositides, markers of organelle identity in the endocytic system. Although many PX domains bind the canonical endosome-enriched lipid PtdIns3P, others interact with alternative phosphoinositides, and a precise understanding of how these specificities arise has remained elusive. Here we systematically screen all human PX domains for their phospholipid preferences using liposome binding assays, biolayer interferometry and isothermal titration calorimetry. These analyses define four distinct classes of human PX domains that either bind specifically to PtdIns3P, non-specifically to various di- and tri-phosphorylated phosphoinositides, bind both PtdIns3P and other phosphoinositides, or associate with none of the lipids tested. A comprehensive evaluation of PX domain structures reveals two distinct binding sites that explain these specificities, providing a basis for defining and predicting the functional membrane interactions of the entire PX domain protein family. Nature Publishing Group UK 2019-04-04 /pmc/articles/PMC6449406/ /pubmed/30948714 http://dx.doi.org/10.1038/s41467-019-09355-y Text en © Crown 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Chandra, Mintu Chin, Yanni K.-Y. Mas, Caroline Feathers, J. Ryan Paul, Blessy Datta, Sanchari Chen, Kai-En Jia, Xinying Yang, Zhe Norwood, Suzanne J. Mohanty, Biswaranjan Bugarcic, Andrea Teasdale, Rohan D. Henne, W. Mike Mobli, Mehdi Collins, Brett M. Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title | Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title_full | Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title_fullStr | Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title_full_unstemmed | Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title_short | Classification of the human phox homology (PX) domains based on their phosphoinositide binding specificities |
title_sort | classification of the human phox homology (px) domains based on their phosphoinositide binding specificities |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449406/ https://www.ncbi.nlm.nih.gov/pubmed/30948714 http://dx.doi.org/10.1038/s41467-019-09355-y |
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