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Title: Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins

Authors:
 [1];  [2];  [3];  [4];  [5]; ORCiD logo [1]
  1. Department of Physiology and BiophysicsWeill Cornell Medical College of Cornell University New York New York 10065, Institute for Computational Biomedicine, Weill Cornell Medical College of Cornell University New York New York 10065
  2. Department of Physiology and BiophysicsWeill Cornell Medical College of Cornell University New York New York 10065
  3. Department of BiochemistryWeill Cornell Medical College of Cornell University New York New York 10065
  4. Department of Integrative Biology and PharmacologyUniversity of Texas Health Science Center at Houston Houston Texas 77030
  5. Department of Physiology and BiophysicsWeill Cornell Medical College of Cornell University New York New York 10065, Department of BiochemistryWeill Cornell Medical College of Cornell University New York New York 10065, Department of AnesthesiologyWeill Cornell Medical College of Cornell University New York New York 10065
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1575104
Resource Type:
Publisher's Accepted Manuscript
Journal Name:
Journal of Computational Chemistry
Additional Journal Information:
Journal Name: Journal of Computational Chemistry; Journal ID: ISSN 0192-8651
Publisher:
Wiley Blackwell (John Wiley & Sons)
Country of Publication:
United States
Language:
English

Citation Formats

Khelashvili, George, Cheng, Xiaolu, Falzone, Maria E., Doktorova, Milka, Accardi, Alessio, and Weinstein, Harel. Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins. United States: N. p., 2019. Web. doi:10.1002/jcc.26105.
Khelashvili, George, Cheng, Xiaolu, Falzone, Maria E., Doktorova, Milka, Accardi, Alessio, & Weinstein, Harel. Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins. United States. doi:10.1002/jcc.26105.
Khelashvili, George, Cheng, Xiaolu, Falzone, Maria E., Doktorova, Milka, Accardi, Alessio, and Weinstein, Harel. Thu . "Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins". United States. doi:10.1002/jcc.26105.
@article{osti_1575104,
title = {Membrane lipids are both the substrates and a mechanistically responsive environment of TMEM16 scramblase proteins},
author = {Khelashvili, George and Cheng, Xiaolu and Falzone, Maria E. and Doktorova, Milka and Accardi, Alessio and Weinstein, Harel},
abstractNote = {},
doi = {10.1002/jcc.26105},
journal = {Journal of Computational Chemistry},
number = ,
volume = ,
place = {United States},
year = {2019},
month = {11}
}

Journal Article:
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Works referenced in this record:

Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels
journal, March 2015

  • Peters, Christian J.; Yu, Haibo; Tien, Jason
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 11
  • DOI: 10.1073/pnas.1502291112

Characterization of the scrambling domain of the TMEM16 family
journal, May 2017

  • Gyobu, Sayuri; Ishihara, Kenji; Suzuki, Jun
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 24
  • DOI: 10.1073/pnas.1703391114

Ligand-Dependent Conformations and Dynamics of the Serotonin 5-HT2A Receptor Determine Its Activation and Membrane-Driven Oligomerization Properties
journal, April 2012


Structural basis of Ca2+-dependent activation and lipid transport by a TMEM16 scramblase
journal, January 2019

  • Falzone, Maria E.; Rheinberger, Jan; Lee, Byoung-Cheol
  • eLife, Vol. 8
  • DOI: 10.7554/eLife.43229

Lipid flippases and their biological functions
journal, November 2006


Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16 scramblase
journal, August 2018


Anoctamins/TMEM16 Proteins: Chloride Channels Flirting with Lipids and Extracellular Vesicles
journal, February 2017


Dynamic modulation of the lipid translocation groove generates a conductive ion channel in Ca2+-bound nhTMEM16
journal, October 2019


A Pore Idea: the ion conduction pathway of TMEM16/ANO proteins is composed partly of lipid
journal, January 2016

  • Whitlock, Jarred M.; Hartzell, H. Criss
  • Pflügers Archiv - European Journal of Physiology, Vol. 468, Issue 3
  • DOI: 10.1007/s00424-015-1777-2

The cost of living in the membrane: A case study of hydrophobic mismatch for the multi-segment protein LeuT
journal, April 2013


Quantitative Modeling of Membrane Deformations by Multihelical Membrane Proteins: Application to G-Protein Coupled Receptors
journal, November 2011


X-ray structure of a calcium-activated TMEM16 lipid scramblase
journal, November 2014

  • Brunner, Janine D.; Lim, Novandy K.; Schenck, Stephan
  • Nature, Vol. 516, Issue 7530
  • DOI: 10.1038/nature13984

G Protein-Coupled Receptors Self-Assemble in Dynamics Simulations of Model Bilayers
journal, August 2007

  • Periole, Xavier; Huber, Thomas; Marrink, Siewert-Jan
  • Journal of the American Chemical Society, Vol. 129, Issue 33
  • DOI: 10.1021/ja0706246

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K
journal, September 2019

  • Bushell, Simon R.; Pike, Ashley C. W.; Falzone, Maria E.
  • Nature Communications, Vol. 10, Issue 1
  • DOI: 10.1038/s41467-019-11753-1

CHARMM-GUI Nanodisc Builder for modeling and simulation of various nanodisc systems : CHARMM-GUI
journal, January 2019

  • Qi, Yifei; Lee, Jumin; Klauda, Jeffery B.
  • Journal of Computational Chemistry, Vol. 40, Issue 7
  • DOI: 10.1002/jcc.25773

Scalable molecular dynamics with NAMD
journal, January 2005

  • Phillips, James C.; Braun, Rosemary; Wang, Wei
  • Journal of Computational Chemistry, Vol. 26, Issue 16, p. 1781-1802
  • DOI: 10.1002/jcc.20289

Identification of a lipid scrambling domain in ANO6/TMEM16F
journal, June 2015


Structural Determinants of the Supramolecular Organization of G Protein-Coupled Receptors in Bilayers
journal, June 2012

  • Periole, Xavier; Knepp, Adam M.; Sakmar, Thomas P.
  • Journal of the American Chemical Society, Vol. 134, Issue 26
  • DOI: 10.1021/ja303286e

Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone ϕ, ψ and Side-Chain χ 1 and χ 2 Dihedral Angles
journal, August 2012

  • Best, Robert B.; Zhu, Xiao; Shim, Jihyun
  • Journal of Chemical Theory and Computation, Vol. 8, Issue 9
  • DOI: 10.1021/ct300400x

Gramicidin Increases Lipid Flip-Flop in Symmetric and Asymmetric Lipid Vesicles
journal, March 2019

  • Doktorova, Milka; Heberle, Frederick A.; Marquardt, Drew
  • Biophysical Journal, Vol. 116, Issue 5
  • DOI: 10.1016/j.bpj.2019.01.016

MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes
journal, July 2015


Simulations of Anionic Lipid Membranes: Development of Interaction-Specific Ion Parameters and Validation Using NMR Data
journal, August 2013

  • Venable, Richard M.; Luo, Yun; Gawrisch, Klaus
  • The Journal of Physical Chemistry B, Vol. 117, Issue 35
  • DOI: 10.1021/jp401512z

Lifting the veils on TMEM16E function
journal, January 2019


How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties
journal, March 2018


Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues
journal, January 2013

  • Ehlen, Harald WA; Chinenkova, Milana; Moser, Markus
  • Journal of Bone and Mineral Research, Vol. 28, Issue 2
  • DOI: 10.1002/jbmr.1751

Contribution of Membrane Elastic Energy to Rhodopsin Function
journal, August 2010


Cryo-EM structures of the TMEM16A calcium-activated chloride channel
journal, December 2017

  • Dang, Shangyu; Feng, Shengjie; Tien, Jason
  • Nature, Vol. 552, Issue 7685
  • DOI: 10.1038/nature25024

Curvature and Hydrophobic Forces Drive Oligomerization and Modulate Activity of Rhodopsin in Membranes
journal, December 2006


The nhTMEM16 Scramblase Is Also a Nonselective Ion Channel
journal, November 2016

  • Lee, Byoung-Cheol; Menon, Anant K.; Accardi, Alessio
  • Biophysical Journal, Vol. 111, Issue 9
  • DOI: 10.1016/j.bpj.2016.09.032

CHARMM-GUI Membrane Builder toward realistic biological membrane simulations
journal, August 2014

  • Wu, Emilia L.; Cheng, Xi; Jo, Sunhwan
  • Journal of Computational Chemistry, Vol. 35, Issue 27
  • DOI: 10.1002/jcc.23702

Stepwise activation mechanism of the scramblase nhTMEM16 revealed by cryo-EM
journal, February 2019

  • Kalienkova, Valeria; Clerico Mosina, Vanessa; Bryner, Laura
  • eLife, Vol. 8
  • DOI: 10.7554/eLife.44364

Membrane Driven Spatial Organization of GPCRs
journal, October 2013

  • Mondal, Sayan; Johnston, Jennifer M.; Wang, Hao
  • Scientific Reports, Vol. 3, Issue 1
  • DOI: 10.1038/srep02909

Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F
journal, February 2019

  • Alvadia, Carolina; Lim, Novandy K.; Clerico Mosina, Vanessa
  • eLife, Vol. 8
  • DOI: 10.7554/eLife.44365

New Continuum Approaches for Determining Protein-Induced Membrane Deformations
journal, May 2017

  • Argudo, David; Bethel, Neville P.; Marcoline, Frank V.
  • Biophysical Journal, Vol. 112, Issue 10
  • DOI: 10.1016/j.bpj.2017.03.040

Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types
journal, June 2010

  • Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo
  • The Journal of Physical Chemistry B, Vol. 114, Issue 23
  • DOI: 10.1021/jp101759q

Ca2+-dependent phospholipid scrambling by a reconstituted TMEM16 ion channel
journal, September 2013

  • Malvezzi, Mattia; Chalat, Madhavan; Janjusevic, Radmila
  • Nature Communications, Vol. 4, Issue 1
  • DOI: 10.1038/ncomms3367

A New Computational Method for Membrane Compressibility: Bilayer Mechanical Thickness Revisited
journal, February 2019

  • Doktorova, Milka; LeVine, Michael V.; Khelashvili, George
  • Biophysical Journal, Vol. 116, Issue 3
  • DOI: 10.1016/j.bpj.2018.12.016

Atomistic insight into lipid translocation by a TMEM16 scramblase
journal, November 2016

  • Bethel, Neville P.; Grabe, Michael
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 49
  • DOI: 10.1073/pnas.1607574113

Mechanisms of Lipid Scrambling by the G Protein-Coupled Receptor Opsin
journal, February 2018


Not Just an Oil Slick: How the Energetics of Protein-Membrane Interactions Impacts the Function and Organization of Transmembrane Proteins
journal, June 2014

  • Mondal, Sayan; Khelashvili, George; Weinstein, Harel
  • Biophysical Journal, Vol. 106, Issue 11
  • DOI: 10.1016/j.bpj.2014.04.032

CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes
journal, July 2009


ACEMD: Accelerating Biomolecular Dynamics in the Microsecond Time Scale
journal, May 2009

  • Harvey, M. J.; Giupponi, G.; Fabritiis, G. De
  • Journal of Chemical Theory and Computation, Vol. 5, Issue 6
  • DOI: 10.1021/ct9000685

Identification of slow molecular order parameters for Markov model construction
journal, July 2013

  • Pérez-Hernández, Guillermo; Paul, Fabian; Giorgino, Toni
  • The Journal of Chemical Physics, Vol. 139, Issue 1
  • DOI: 10.1063/1.4811489

A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter
journal, January 2017

  • Razavi, Asghar M.; Khelashvili, George; Weinstein, Harel
  • Scientific Reports, Vol. 7, Issue 1
  • DOI: 10.1038/srep40076

Known structures and unknown mechanisms of TMEM16 scramblases and channels
journal, June 2018

  • Falzone, Maria E.; Malvezzi, Mattia; Lee, Byoung-Cheol
  • The Journal of General Physiology, Vol. 150, Issue 7
  • DOI: 10.1085/jgp.201711957

Anoctamins (TMEM16 proteins): Functions and involvement in neurologic disease
journal, July 2017