Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes

Neurofibromatosis type 2 is an inherited autosomal disorder caused by biallelic inactivation of the NF2 tumor suppressor gene. The NF2 gene encodes a 70-kDa protein, merlin, which is a member of the ezrin-radixin-moesin (ERM) family. ERM proteins are believed to be regulated by a transition between...

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Main Authors:	Hennigan, Robert F., Foster, Lauren A., Chaiken, Mary F., Mani, Timmy, Gomes, Michelle M., Herr, Andrew B., Ip, Wallace
Formato:	Artigo
Idioma:	Inglês
Publicado em:	American Society for Microbiology (ASM) 2010
Assuntos:	Articles
Acesso em linha:	https://ncbi.nlm.nih.gov/pmc/articles/PMC2798298/ https://ncbi.nlm.nih.gov/pubmed/19884346 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/MCB.00248-09
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spelling	pubmed-27982982010-07-01 Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes Hennigan, Robert F. Foster, Lauren A. Chaiken, Mary F. Mani, Timmy Gomes, Michelle M. Herr, Andrew B. Ip, Wallace Mol Cell Biol Articles Neurofibromatosis type 2 is an inherited autosomal disorder caused by biallelic inactivation of the NF2 tumor suppressor gene. The NF2 gene encodes a 70-kDa protein, merlin, which is a member of the ezrin-radixin-moesin (ERM) family. ERM proteins are believed to be regulated by a transition between a closed conformation, formed by binding of their N-terminal FERM domain and C-terminal tail domain (CTD), and an open conformation, in which the two domains do not interact. Previous work suggests that the tumor suppressor function of merlin is similarly regulated and that only the closed form is active. Therefore, understanding the mechanisms that control its conformation is crucial. We have developed a series of probes that measures merlin conformation by fluorescence resonance energy transfer, both as purified protein and in live cells. Using these tools, we find that merlin exists predominately as a monomer in a stable, closed conformation that is mediated by the central α-helical domain. The contribution from the FERM-CTD interaction to the closed conformation appears to be less important. Upon phosphorylation or interaction with an effector protein, merlin undergoes a subtle conformational change, suggesting a novel mechanism that modulates the interaction between the FERM domain and the CTD. American Society for Microbiology (ASM) 2010-01 2009-11-02 /pmc/articles/PMC2798298/ /pubmed/19884346 http://dx.doi.org/10.1128/MCB.00248-09 Text en Copyright © 2010, American Society for Microbiology
institution	US NLM
collection	PubMed Central
language	Inglês
format	Artigo
topic	Articles
spellingShingle	Articles Hennigan, Robert F. Foster, Lauren A. Chaiken, Mary F. Mani, Timmy Gomes, Michelle M. Herr, Andrew B. Ip, Wallace Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
description	Neurofibromatosis type 2 is an inherited autosomal disorder caused by biallelic inactivation of the NF2 tumor suppressor gene. The NF2 gene encodes a 70-kDa protein, merlin, which is a member of the ezrin-radixin-moesin (ERM) family. ERM proteins are believed to be regulated by a transition between a closed conformation, formed by binding of their N-terminal FERM domain and C-terminal tail domain (CTD), and an open conformation, in which the two domains do not interact. Previous work suggests that the tumor suppressor function of merlin is similarly regulated and that only the closed form is active. Therefore, understanding the mechanisms that control its conformation is crucial. We have developed a series of probes that measures merlin conformation by fluorescence resonance energy transfer, both as purified protein and in live cells. Using these tools, we find that merlin exists predominately as a monomer in a stable, closed conformation that is mediated by the central α-helical domain. The contribution from the FERM-CTD interaction to the closed conformation appears to be less important. Upon phosphorylation or interaction with an effector protein, merlin undergoes a subtle conformational change, suggesting a novel mechanism that modulates the interaction between the FERM domain and the CTD.
author	Hennigan, Robert F. Foster, Lauren A. Chaiken, Mary F. Mani, Timmy Gomes, Michelle M. Herr, Andrew B. Ip, Wallace
author_facet	Hennigan, Robert F. Foster, Lauren A. Chaiken, Mary F. Mani, Timmy Gomes, Michelle M. Herr, Andrew B. Ip, Wallace
author_sort	Hennigan, Robert F.
title	Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
title_short	Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
title_full	Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
title_fullStr	Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
title_full_unstemmed	Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes
title_sort	fluorescence resonance energy transfer analysis of merlin conformational changes
publisher	American Society for Microbiology (ASM)
publishDate	2010
url	https://ncbi.nlm.nih.gov/pmc/articles/PMC2798298/ https://ncbi.nlm.nih.gov/pubmed/19884346 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1128/MCB.00248-09
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Fluorescence Resonance Energy Transfer Analysis of Merlin Conformational Changes

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