@article{fa55e181540445ddb999b619797dd8d6,
title = "Cryo-em structure of mechanosensitive channel ynai using sma2000: Challenges and opportunities",
abstract = "Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. High-resolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, the complete structure of the transmembrane domain of YnaI was not resolved. This reveals a significant limitation of SMA2000 or similar membrane-active copolymers. This limitation may come from the heterogeneity of the polymers and nonspecific interactions between the polymers and the relatively large hydrophobic pockets within the transmembrane domain of YnaI. However, this limitation offers development opportunities for detergent-free technology for challenging membrane proteins.",
keywords = "Cryo-EM, Mechanosensitive Channel, NCMN, SMA2000, YnaI",
author = "Claudio Catalano and Danya Ben-Hail and Weihua Qiu and Paul Blount and {des Georges}, Amedee and Youzhong Guo",
note = "Funding Information: Acknowledgments: Some of this work was performed at the National Center for Cryo-EM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High-Resolution Cryo-Electron Microscopy program (U24 GM129539), and by grants from the Simons Foundation (SF349247) and NY State Assembly. We thank Tong Wang at CUNY Advanced Science Research Center for help in sample screening, Ed Eng, Charlie Dubbeldam, Elina Kopylov, Carolina Hernandez, Kashyap Maruthi, and others at the Simons Electron Microscopy Center (SEMC) and New York Structural Biology Center (NYSBC) for help in data collection, and Glen E. Kellogg, Irene Iscla, and Harsh Bansia for critical reading of the manuscript. Funding Information: Funding: Y.G. was supported by the VCU School of Pharmacy and Department of Medicinal Chemistry through startup funds, the Institute for Structural Biology, Drug Discovery and Development through laboratory space and facilities, and NIH Grant R01-GM132329. A.G. was supported by NIH grant R35GM133598. P.B. was supported by Grant I-1420 of the Welch Foundation and GM121780 from the National Institutes of Health (NIH). The funders had no role in study design, data collection, analysis, decision to publish, or manuscript preparation. The content is solely the authors{\textquoteright} responsibility and does not necessarily represent the National Institutes of Health or other funding organizations{\textquoteright} official views. Funding Information: Y.G. was supported by the VCU School of Pharmacy and Department of Medicinal Chemistry through startup funds, the Institute for Structural Biology, Drug Discovery and Development through laboratory space and facilities, and NIH Grant R01-GM132329. A.G. was supported by NIH grant R35GM133598. P.B. was supported by Grant I-1420 of the Welch Foundation and GM121780 from the National Institutes of Health (NIH). The funders had no role in study design, data col-lection, analysis, decision to publish, or manuscript preparation. The content is solely the authors? responsibility and does not necessarily represent the National Institutes of Health or other funding organizations? official views. Acknowledgments: Some of this work was performed at the National Center for Cryo-EM Access and Training (NCCAT) and the Simons Electron Microscopy Center located at the New York Structural Biology Center, supported by the NIH Common Fund Transformative High-Resolution Cryo-Electron Microscopy program (U24 GM129539), and by grants from the Simons Foundation (SF349247) and NY State Assembly. We thank Tong Wang at CUNY Advanced Science Research Center for help in sample screening, Ed Eng, Charlie Dubbeldam, Elina Kopylov, Carolina Hernandez, Kashyap Maruthi, and others at the Simons Electron Microscopy Center (SEMC) and New York Structural Biology Center (NYSBC) for help in data collection, and Glen E. Kellogg, Irene Iscla, and Harsh Bansia for critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = nov,
doi = "10.3390/membranes11110849",
language = "English (US)",
volume = "11",
journal = "Membranes",
issn = "2077-0375",
publisher = "Molecular Diversity Preservation International",
number = "11",
}