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Structure of a tetrameric MscL in an expanded intermediate state

The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation1, 2. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassiu...

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Autores principales: Liu, Zhenfeng, Gandhi, Chris S., Rees, Douglas C.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737600/
https://www.ncbi.nlm.nih.gov/pubmed/19701184
http://dx.doi.org/10.1038/nature08277
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author Liu, Zhenfeng
Gandhi, Chris S.
Rees, Douglas C.
author_facet Liu, Zhenfeng
Gandhi, Chris S.
Rees, Douglas C.
author_sort Liu, Zhenfeng
collection PubMed
description The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation1, 2. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK), and mini (MscM) conductances. These channels act as “emergency relief valves” protecting bacteria from lysis upon acute osmotic downshock3. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago by Kung and co-workers4. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a nonselective 3 nS-conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 Å resolution of a pentameric MscL from Mycobacterium tuberculosis (TbMscL) represents a closed-state or nonconducting conformation5, 6. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative nonconductive expanded state and at least three sub-conducting states7. Although our understanding of the closed5, 6 and open8-10 states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a truncation mutant (Δ95-120) of MscL from Staphylococcus aureus (SaMscL-CΔ26) at 3.8 Å resolution. Strikingly, SaMscL-CΔ26 forms a tetrameric channel with both transmembrane (TM) helices tilted away from the membrane normal at angles close to that inferred for the open state9, likely corresponding to a nonconductive but partially expanded intermediate state.
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spelling pubmed-27376002010-03-03 Structure of a tetrameric MscL in an expanded intermediate state Liu, Zhenfeng Gandhi, Chris S. Rees, Douglas C. Nature Article The ability of cells to sense and respond to mechanical force underlies diverse processes such as touch and hearing in animals, gravitropism in plants, and bacterial osmoregulation1, 2. In bacteria, mechanosensation is mediated by the mechanosensitive channels of large (MscL), small (MscS), potassium-dependent (MscK), and mini (MscM) conductances. These channels act as “emergency relief valves” protecting bacteria from lysis upon acute osmotic downshock3. Among them, MscL has been intensively studied since the original identification and characterization 15 years ago by Kung and co-workers4. MscL is reversibly and directly gated by changes in membrane tension. In the open state, MscL forms a nonselective 3 nS-conductance channel which gates at tensions close to the lytic limit of the bacterial membrane. An earlier crystal structure at 3.5 Å resolution of a pentameric MscL from Mycobacterium tuberculosis (TbMscL) represents a closed-state or nonconducting conformation5, 6. MscL has a complex gating behaviour; it exhibits several intermediates between the closed and open states, including one putative nonconductive expanded state and at least three sub-conducting states7. Although our understanding of the closed5, 6 and open8-10 states of MscL has been increasing, little is known about the structures of the intermediate states despite their importance in elucidating the complete gating process of MscL. Here we present the crystal structure of a truncation mutant (Δ95-120) of MscL from Staphylococcus aureus (SaMscL-CΔ26) at 3.8 Å resolution. Strikingly, SaMscL-CΔ26 forms a tetrameric channel with both transmembrane (TM) helices tilted away from the membrane normal at angles close to that inferred for the open state9, likely corresponding to a nonconductive but partially expanded intermediate state. 2009-08-23 2009-09-03 /pmc/articles/PMC2737600/ /pubmed/19701184 http://dx.doi.org/10.1038/nature08277 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Liu, Zhenfeng
Gandhi, Chris S.
Rees, Douglas C.
Structure of a tetrameric MscL in an expanded intermediate state
title Structure of a tetrameric MscL in an expanded intermediate state
title_full Structure of a tetrameric MscL in an expanded intermediate state
title_fullStr Structure of a tetrameric MscL in an expanded intermediate state
title_full_unstemmed Structure of a tetrameric MscL in an expanded intermediate state
title_short Structure of a tetrameric MscL in an expanded intermediate state
title_sort structure of a tetrameric mscl in an expanded intermediate state
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737600/
https://www.ncbi.nlm.nih.gov/pubmed/19701184
http://dx.doi.org/10.1038/nature08277
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