A dual binding mode for RhoGTPases in plexin signalling.

Plexins are cell surface receptors for the semaphorin family of cell guidance cues. The cytoplasmic region comprises a Ras GTPase-activating protein (GAP) domain and a RhoGTPase binding domain. Concomitant binding of extracellular semaphorin and intracellular RhoGTPase triggers GAP activity and sign...

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Autores principales:	Christian H Bell, A Radu Aricescu, E Yvonne Jones, Christian Siebold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/802b9e5141fe449e9c5be833e0a97e31
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spelling	oai:doaj.org-article:802b9e5141fe449e9c5be833e0a97e312021-11-18T05:36:02ZA dual binding mode for RhoGTPases in plexin signalling.1544-91731545-788510.1371/journal.pbio.1001134https://doaj.org/article/802b9e5141fe449e9c5be833e0a97e312011-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21912513/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Plexins are cell surface receptors for the semaphorin family of cell guidance cues. The cytoplasmic region comprises a Ras GTPase-activating protein (GAP) domain and a RhoGTPase binding domain. Concomitant binding of extracellular semaphorin and intracellular RhoGTPase triggers GAP activity and signal transduction. The mechanism of this intricate regulation remains elusive. We present two crystal structures of the human Plexin-B1 cytoplasmic region in complex with a constitutively active RhoGTPase, Rac1. The structure of truncated Plexin-B1-Rac1 complex provides no mechanism for coupling RhoGTPase and Ras binding sites. On inclusion of the juxtamembrane helix, a trimeric structure of Plexin-B1-Rac1 complexes is stabilised by a second, novel, RhoGTPase binding site adjacent to the Ras site. Site-directed mutagenesis combined with cellular and biophysical assays demonstrate that this new binding site is essential for signalling. Our findings are consistent with a model in which extracellular and intracellular plexin clustering events combine into a single signalling output.Christian H BellA Radu AricescuE Yvonne JonesChristian SieboldPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 9, Iss 8, p e1001134 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Christian H Bell A Radu Aricescu E Yvonne Jones Christian Siebold A dual binding mode for RhoGTPases in plexin signalling.
description	Plexins are cell surface receptors for the semaphorin family of cell guidance cues. The cytoplasmic region comprises a Ras GTPase-activating protein (GAP) domain and a RhoGTPase binding domain. Concomitant binding of extracellular semaphorin and intracellular RhoGTPase triggers GAP activity and signal transduction. The mechanism of this intricate regulation remains elusive. We present two crystal structures of the human Plexin-B1 cytoplasmic region in complex with a constitutively active RhoGTPase, Rac1. The structure of truncated Plexin-B1-Rac1 complex provides no mechanism for coupling RhoGTPase and Ras binding sites. On inclusion of the juxtamembrane helix, a trimeric structure of Plexin-B1-Rac1 complexes is stabilised by a second, novel, RhoGTPase binding site adjacent to the Ras site. Site-directed mutagenesis combined with cellular and biophysical assays demonstrate that this new binding site is essential for signalling. Our findings are consistent with a model in which extracellular and intracellular plexin clustering events combine into a single signalling output.
format	article
author	Christian H Bell A Radu Aricescu E Yvonne Jones Christian Siebold
author_facet	Christian H Bell A Radu Aricescu E Yvonne Jones Christian Siebold
author_sort	Christian H Bell
title	A dual binding mode for RhoGTPases in plexin signalling.
title_short	A dual binding mode for RhoGTPases in plexin signalling.
title_full	A dual binding mode for RhoGTPases in plexin signalling.
title_fullStr	A dual binding mode for RhoGTPases in plexin signalling.
title_full_unstemmed	A dual binding mode for RhoGTPases in plexin signalling.
title_sort	dual binding mode for rhogtpases in plexin signalling.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/802b9e5141fe449e9c5be833e0a97e31
work_keys_str_mv	AT christianhbell adualbindingmodeforrhogtpasesinplexinsignalling AT araduaricescu adualbindingmodeforrhogtpasesinplexinsignalling AT eyvonnejones adualbindingmodeforrhogtpasesinplexinsignalling AT christiansiebold adualbindingmodeforrhogtpasesinplexinsignalling AT christianhbell dualbindingmodeforrhogtpasesinplexinsignalling AT araduaricescu dualbindingmodeforrhogtpasesinplexinsignalling AT eyvonnejones dualbindingmodeforrhogtpasesinplexinsignalling AT christiansiebold dualbindingmodeforrhogtpasesinplexinsignalling
_version_	1718424922084081664

A dual binding mode for RhoGTPases in plexin signalling.

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