The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function

Abstract HD-PTP is a tumour suppressor phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that ena...

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Autores principales:	Deepankar Gahloth, Graham Heaven, Thomas A. Jowitt, A. Paul Mould, Jordi Bella, Clair Baldock, Philip Woodman, Lydia Tabernero
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb9b761d30ea4a3cbb093b0b72f678dd
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spelling	oai:doaj.org-article:fb9b761d30ea4a3cbb093b0b72f678dd2021-12-02T11:52:18ZThe open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function10.1038/s41598-017-09467-92045-2322https://doaj.org/article/fb9b761d30ea4a3cbb093b0b72f678dd2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09467-9https://doaj.org/toc/2045-2322Abstract HD-PTP is a tumour suppressor phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that enable HD-PTP to regulate ESCRT function are unknown. We have characterised the molecular architecture of the entire ESCRT binding region of HD-PTP using small angle X-ray scattering and hydrodynamic analyses. We show that HD-PTP adopts an open and extended conformation, optimal for concomitant interactions with multiple ESCRTs, which contrasts with the compact conformation of the related ESCRT regulator Alix. We demonstrate that the HD-PTP open conformation is functionally competent for binding cellular protein partners. Our analyses rationalise the functional cooperation of HD-PTP with ESCRT-0, ESCRT-I and ESCRT-III and support a model for regulation of ESCRT function by displacement of ESCRT subunits, which is crucial in determining the fate of ubiquitinated cargo.Deepankar GahlothGraham HeavenThomas A. JowittA. Paul MouldJordi BellaClair BaldockPhilip WoodmanLydia TaberneroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Deepankar Gahloth Graham Heaven Thomas A. Jowitt A. Paul Mould Jordi Bella Clair Baldock Philip Woodman Lydia Tabernero The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
description	Abstract HD-PTP is a tumour suppressor phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that enable HD-PTP to regulate ESCRT function are unknown. We have characterised the molecular architecture of the entire ESCRT binding region of HD-PTP using small angle X-ray scattering and hydrodynamic analyses. We show that HD-PTP adopts an open and extended conformation, optimal for concomitant interactions with multiple ESCRTs, which contrasts with the compact conformation of the related ESCRT regulator Alix. We demonstrate that the HD-PTP open conformation is functionally competent for binding cellular protein partners. Our analyses rationalise the functional cooperation of HD-PTP with ESCRT-0, ESCRT-I and ESCRT-III and support a model for regulation of ESCRT function by displacement of ESCRT subunits, which is crucial in determining the fate of ubiquitinated cargo.
format	article
author	Deepankar Gahloth Graham Heaven Thomas A. Jowitt A. Paul Mould Jordi Bella Clair Baldock Philip Woodman Lydia Tabernero
author_facet	Deepankar Gahloth Graham Heaven Thomas A. Jowitt A. Paul Mould Jordi Bella Clair Baldock Philip Woodman Lydia Tabernero
author_sort	Deepankar Gahloth
title	The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
title_short	The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
title_full	The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
title_fullStr	The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
title_full_unstemmed	The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
title_sort	open architecture of hd-ptp phosphatase provides new insights into the mechanism of regulation of escrt function
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fb9b761d30ea4a3cbb093b0b72f678dd
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The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function

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