The MscS-like channel YnaI has a gating mechanism based on flexible pore helices
V. Flegler, A. Rasmussen, S. Rao, N. Wu, R. Zenobi, M. Sansom, R. Hedrich, T. Rasmussen, and B. Bottcher. Proc Natl Acad Sci U S A, 117 (46):
28754-28762(2020)Flegler, Vanessa Judith
Rasmussen, Akiko
Rao, Shanlin
Wu, Na
Zenobi, Renato
Sansom, Mark S P
Hedrich, Rainer
Rasmussen, Tim
Bottcher, Bettina
eng
WT_/Wellcome Trust/United Kingdom
208361/Z/17/Z/WT_/Wellcome Trust/United Kingdom
BB/N000145/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
Research Support, Non-U.S. Gov't
2020/11/06
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28754-28762. doi: 10.1073/pnas.2005641117. Epub 2020 Nov 4..
DOI: 10.1073/pnas.2005641117
Abstract
The mechanosensitive channel of small conductance (MscS) is the prototype of an evolutionarily diversified large family that fine-tunes osmoregulation but is likely to fulfill additional functions. Escherichia coli has six osmoprotective paralogs with different numbers of transmembrane helices. These helices are important for gating and sensing in MscS but the role of the additional helices in the paralogs is not understood. The medium-sized channel YnaI was extracted and delivered in native nanodiscs in closed-like and open-like conformations using the copolymer diisobutylene/maleic acid (DIBMA) for structural studies. Here we show by electron cryomicroscopy that YnaI has an extended sensor paddle that during gating relocates relative to the pore concomitant with bending of a GGxGG motif in the pore helices. YnaI is the only one of the six paralogs that has this GGxGG motif allowing the sensor paddle to move outward. Access to the pore is through a vestibule on the cytosolic side that is fenestrated by side portals. In YnaI, these portals are obstructed by aromatic side chains but are still fully hydrated and thus support conductance. For comparison with large-sized channels, we determined the structure of YbiO, which showed larger portals and a wider pore with no GGxGG motif. Further in silico comparison of MscS, YnaI, and YbiO highlighted differences in the hydrophobicity and wettability of their pores and vestibule interiors. Thus, MscS-like channels of different sizes have a common core architecture but show different gating mechanisms and fine-tuned conductive properties.
Flegler, Vanessa Judith
Rasmussen, Akiko
Rao, Shanlin
Wu, Na
Zenobi, Renato
Sansom, Mark S P
Hedrich, Rainer
Rasmussen, Tim
Bottcher, Bettina
eng
WT_/Wellcome Trust/United Kingdom
208361/Z/17/Z/WT_/Wellcome Trust/United Kingdom
BB/N000145/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
Research Support, Non-U.S. Gov't
2020/11/06
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28754-28762. doi: 10.1073/pnas.2005641117. Epub 2020 Nov 4.
%0 Journal Article
%1 flegler2020mscslike
%A Flegler, V. J.
%A Rasmussen, A.
%A Rao, S.
%A Wu, N.
%A Zenobi, R.
%A Sansom, M. S. P.
%A Hedrich, R.
%A Rasmussen, T.
%A Bottcher, B.
%D 2020
%J Proc Natl Acad Sci U S A
%K Cryoelectron Microscopy myOwn uni_network
%N 46
%P 28754-28762
%R 10.1073/pnas.2005641117
%T The MscS-like channel YnaI has a gating mechanism based on flexible pore helices
%U https://www.ncbi.nlm.nih.gov/pubmed/33148804https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682570/pdf/pnas.202005641.pdf
%V 117
%X The mechanosensitive channel of small conductance (MscS) is the prototype of an evolutionarily diversified large family that fine-tunes osmoregulation but is likely to fulfill additional functions. Escherichia coli has six osmoprotective paralogs with different numbers of transmembrane helices. These helices are important for gating and sensing in MscS but the role of the additional helices in the paralogs is not understood. The medium-sized channel YnaI was extracted and delivered in native nanodiscs in closed-like and open-like conformations using the copolymer diisobutylene/maleic acid (DIBMA) for structural studies. Here we show by electron cryomicroscopy that YnaI has an extended sensor paddle that during gating relocates relative to the pore concomitant with bending of a GGxGG motif in the pore helices. YnaI is the only one of the six paralogs that has this GGxGG motif allowing the sensor paddle to move outward. Access to the pore is through a vestibule on the cytosolic side that is fenestrated by side portals. In YnaI, these portals are obstructed by aromatic side chains but are still fully hydrated and thus support conductance. For comparison with large-sized channels, we determined the structure of YbiO, which showed larger portals and a wider pore with no GGxGG motif. Further in silico comparison of MscS, YnaI, and YbiO highlighted differences in the hydrophobicity and wettability of their pores and vestibule interiors. Thus, MscS-like channels of different sizes have a common core architecture but show different gating mechanisms and fine-tuned conductive properties.
@article{flegler2020mscslike,
abstract = {The mechanosensitive channel of small conductance (MscS) is the prototype of an evolutionarily diversified large family that fine-tunes osmoregulation but is likely to fulfill additional functions. Escherichia coli has six osmoprotective paralogs with different numbers of transmembrane helices. These helices are important for gating and sensing in MscS but the role of the additional helices in the paralogs is not understood. The medium-sized channel YnaI was extracted and delivered in native nanodiscs in closed-like and open-like conformations using the copolymer diisobutylene/maleic acid (DIBMA) for structural studies. Here we show by electron cryomicroscopy that YnaI has an extended sensor paddle that during gating relocates relative to the pore concomitant with bending of a GGxGG motif in the pore helices. YnaI is the only one of the six paralogs that has this GGxGG motif allowing the sensor paddle to move outward. Access to the pore is through a vestibule on the cytosolic side that is fenestrated by side portals. In YnaI, these portals are obstructed by aromatic side chains but are still fully hydrated and thus support conductance. For comparison with large-sized channels, we determined the structure of YbiO, which showed larger portals and a wider pore with no GGxGG motif. Further in silico comparison of MscS, YnaI, and YbiO highlighted differences in the hydrophobicity and wettability of their pores and vestibule interiors. Thus, MscS-like channels of different sizes have a common core architecture but show different gating mechanisms and fine-tuned conductive properties.},
added-at = {2024-02-15T15:11:54.000+0100},
author = {Flegler, V. J. and Rasmussen, A. and Rao, S. and Wu, N. and Zenobi, R. and Sansom, M. S. P. and Hedrich, R. and Rasmussen, T. and Bottcher, B.},
biburl = {https://www.bibsonomy.org/bibtex/205cf194c0e5a5706ce1e3aec31dfdc96/jvsi_all},
doi = {10.1073/pnas.2005641117},
interhash = {190273669b7898ebb83ff91a6ca6b56c},
intrahash = {05cf194c0e5a5706ce1e3aec31dfdc96},
issn = {1091-6490 (Electronic)
0027-8424 (Print)
0027-8424 (Linking)},
journal = {Proc Natl Acad Sci U S A},
keywords = {Cryoelectron Microscopy myOwn uni_network},
note = {Flegler, Vanessa Judith
Rasmussen, Akiko
Rao, Shanlin
Wu, Na
Zenobi, Renato
Sansom, Mark S P
Hedrich, Rainer
Rasmussen, Tim
Bottcher, Bettina
eng
WT_/Wellcome Trust/United Kingdom
208361/Z/17/Z/WT_/Wellcome Trust/United Kingdom
BB/N000145/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom
Research Support, Non-U.S. Gov't
2020/11/06
Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28754-28762. doi: 10.1073/pnas.2005641117. Epub 2020 Nov 4.},
number = 46,
pages = {28754-28762},
timestamp = {2024-02-15T15:11:54.000+0100},
title = {The MscS-like channel YnaI has a gating mechanism based on flexible pore helices},
type = {Journal Article},
url = {https://www.ncbi.nlm.nih.gov/pubmed/33148804https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682570/pdf/pnas.202005641.pdf},
volume = 117,
year = 2020
}