Publication

Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F

Alvadia, C., Lim, N. K., Mosina, V. C., Oostergetel, G. T., Dutzler, R. & Paulino, C., 20-Feb-2019, In : eLife. 8, 28 p., 44365.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Alvadia, C., Lim, N. K., Mosina, V. C., Oostergetel, G. T., Dutzler, R., & Paulino, C. (2019). Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. eLife, 8, [44365]. https://doi.org/10.7554/eLife.44365

Author

Alvadia, Carolina ; Lim, Novandy K. ; Mosina, Vanessa Clerico ; Oostergetel, Gert T. ; Dutzler, Raimund ; Paulino, Cristina. / Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. In: eLife. 2019 ; Vol. 8.

Harvard

Alvadia, C, Lim, NK, Mosina, VC, Oostergetel, GT, Dutzler, R & Paulino, C 2019, 'Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F', eLife, vol. 8, 44365. https://doi.org/10.7554/eLife.44365

Standard

Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. / Alvadia, Carolina; Lim, Novandy K.; Mosina, Vanessa Clerico; Oostergetel, Gert T.; Dutzler, Raimund; Paulino, Cristina.

In: eLife, Vol. 8, 44365, 20.02.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Alvadia C, Lim NK, Mosina VC, Oostergetel GT, Dutzler R, Paulino C. Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. eLife. 2019 Feb 20;8. 44365. https://doi.org/10.7554/eLife.44365


BibTeX

@article{e2d5a647671b427181c8470057ca4d74,
title = "Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F",
abstract = "The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel. The cryo-EM data of mTMEM16F in absence and presence of Ca2+ define the ligand-free closed conformation of the protein and the structure of a Ca2+ -bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, both functions appear to be mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.",
keywords = "INDEPENDENT ACTIVATION, ION-CHANNEL, CALCIUM, MECHANISMS, PROTEINS, PHOSPHATIDYLSERINE, RECONSTITUTION, VISUALIZATION, EXPRESSION, RESOLUTION",
author = "Carolina Alvadia and Lim, {Novandy K.} and Mosina, {Vanessa Clerico} and Oostergetel, {Gert T.} and Raimund Dutzler and Cristina Paulino",
year = "2019",
month = "2",
day = "20",
doi = "10.7554/eLife.44365",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "ELIFE SCIENCES PUBLICATIONS LTD",

}

RIS

TY - JOUR

T1 - Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F

AU - Alvadia, Carolina

AU - Lim, Novandy K.

AU - Mosina, Vanessa Clerico

AU - Oostergetel, Gert T.

AU - Dutzler, Raimund

AU - Paulino, Cristina

PY - 2019/2/20

Y1 - 2019/2/20

N2 - The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel. The cryo-EM data of mTMEM16F in absence and presence of Ca2+ define the ligand-free closed conformation of the protein and the structure of a Ca2+ -bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, both functions appear to be mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.

AB - The lipid scramblase TMEM16F initiates blood coagulation by catalyzing the exposure of phosphatidylserine in platelets. The protein is part of a family of membrane proteins, which encompasses calcium-activated channels for ions and lipids. Here, we reveal features of murine TMEM16F (mTMEM16F) that underlie its function as a lipid scramblase and an ion channel. The cryo-EM data of mTMEM16F in absence and presence of Ca2+ define the ligand-free closed conformation of the protein and the structure of a Ca2+ -bound intermediate. Both conformations resemble their counterparts of the scrambling-incompetent anion channel mTMEM16A, yet with distinct differences in the region of ion and lipid permeation. In conjunction with functional data, we demonstrate the relationship between ion conduction and lipid scrambling. Although activated by a common mechanism, both functions appear to be mediated by alternate protein conformations that are at equilibrium in the ligand-bound state.

KW - INDEPENDENT ACTIVATION

KW - ION-CHANNEL

KW - CALCIUM

KW - MECHANISMS

KW - PROTEINS

KW - PHOSPHATIDYLSERINE

KW - RECONSTITUTION

KW - VISUALIZATION

KW - EXPRESSION

KW - RESOLUTION

U2 - 10.7554/eLife.44365

DO - 10.7554/eLife.44365

M3 - Article

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

M1 - 44365

ER -

ID: 95844393