scholarly journals Lipid fingerprints are similar between SLC6 transporters in the neuronal membrane

2021 ◽  
Author(s):  
Katie A. Wilson ◽  
Lily Wang ◽  
Yie Chang Lin ◽  
Megan L. O’Mara
Keyword(s):  
Protein Interactions ◽  
Neuronal Membrane ◽  
List Type ◽  
Membrane Composition ◽  
Biophysical Properties ◽  
Complex Membrane ◽  
Lipid Environment ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
Specific Lipid

ABSTRACTWe use molecular dynamics simulations to characterise the local lipid annulus, or “fingerprint”, of three SLC6 transporters (dDAT, hSERT, and GlyT2) embedded into a complex neuronal membrane. New membrane analysis tools were created to improve leaflet detection and leaflet-dependent properties. Overall, lipid fingerprints are comprised of similar lipids when grouped by headgroup or tail saturation. The enrichment and depletion of specific lipids, including sites of cholesterol contacts, varies between transporters. The subtle differences in lipid fingerprints results in varying membrane biophysical properties near the transporter. Through comparisons to previous literature, we highlight that the lipid-fingerprint in complex membranes is highly dependent on membrane composition. Furthermore, through embedding these transporters in a simplified model membrane, we show that the simplified membrane is not able to capture the biophysical properties of the complex membrane. Our results further characterise how the presence and identity of membrane proteins affects the complex interplay of lipid-protein interactions, including the local lipid environment and membrane biophysical properties.HIGHLIGHTSLipid fingerprints are comprised of similar lipid classesSites of specific lipid contacts, including CHOL, varies between transportersChanges in lipid annulus result in variable local membrane biophysical propertiesMembrane composition, including that of complex membranes, affects lipid annulusGRAPHICAL ABSTRACT

scholarly journals Lipid-protein interactions are unique fingerprints for membrane proteins

2017 ◽  
Author(s):  
Valentina Corradi ◽  
Eduardo Mendez-Villuendas ◽  
Helgi I. Ingólfsson ◽  
Ruo-Xu Gu ◽  
Iwona Siuda ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Cell Membranes ◽  
Spatiotemporal Resolution ◽  
Lipid Dynamics ◽  
Lipid Species ◽  
Lipid Environment ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
Asymmetrically Distributed

ABSTRACTCell membranes contain hundreds of different proteins and lipids in an asymmetric arrangement. Understanding the lateral organization principles of these complex mixtures is essential for life and health. However, our current understanding of the detailed organization of cell membranes remains rather elusive, owing to the lack of experimental methods suitable for studying these fluctuating nanoscale assemblies of lipids and proteins with the required spatiotemporal resolution. Here, we use molecular dynamics simulations to characterize the lipid environment of ten membrane proteins. To provide a realistic lipid environment, the proteins are embedded in a model plasma membrane, where more than 60 lipid species are represented, asymmetrically distributed between leaflets. The simulations detail how each protein modulates its local lipid environment through local lipid composition, thickness, curvature and lipid dynamics. Our results provide a molecular glimpse of the complexity of lipid-protein interactions, with potentially far reaching implications for the overall organization of the cell membrane.

scholarly journals State-dependent protein-lipid interactions of a pentameric ligand-gated ion channel in a neuronal membrane

2020 ◽  
Author(s):  
Marc A. Dämgen ◽  
Philip C. Biggin
Keyword(s):  
Ion Channels ◽  
Protein Interactions ◽  
Glycine Receptor ◽  
Realistic Model ◽  
Neuronal Membrane ◽  
Lipid Interactions ◽  
State Dependent ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
A Site

AbstractPentameric ligand-gated ion channels (pLGICs) are receptor proteins that are sensitive to their membrane environment, but the mechanism for how lipids modulate function under physiological conditions in a state dependent manner is not known. The glycine receptor is a pLGIC whose structure has been resolved in different functional states. Using a realistic model of a neuronal membrane coupled with coarse-grained molecular dynamics simulations, we demonstrate that the lipid-protein interactions are dependent on the receptor state, suggesting that lipids may regulate the receptor’s conformational dynamics. Comparison with existing structural data confirms known lipid binding sites, but we also predict further protein-lipid interactions including a site at the communication interface between the extracellular and transmembrane domain. Moreover, in the active state, cholesterol can bind to the binding site of the positive allosteric modulator ivermectin. These protein-lipid interaction sites could in future be exploited for the rational design of lipid-like allosteric drugs.Author SummaryIon channels are proteins that control the flow of ions into the cell. The family of ion channels known as the pentameric ligand gated ion channels (pLGICS) open in response to the binding of a neurotransmitter, moving the channel from a resting state to an open state. The glycine receptor is a pLGIC whose structure has been resolved in different functional states. It is also known that the response of pLGICs can also be modified by different types of lipid found within the membrane itself but exactly how is unclear. Here, we used a realistic model of a neuronal membrane and performed molecular dynamics simulations to show various lipid-protein interactions that are dependent on the channel state. Our work also reveals previously unconsidered protein-lipid interactions at a key junction of the channel known to be critical for the transmission of the opening process. We also demonstrate that cholesterol interacts with the protein at a site already known to bind to another compound that modulates the channel, called ivermectin. The work should be useful for future drug design.

scholarly journals Curvature and Specific Lipid-Protein Interactions Modulate Activity of Rhodopsin

2009 ◽  
Vol 96 (3) ◽  
pp. 378a
Author(s):  
Olivier Soubias ◽  
Shui-Lin Niu ◽  
Drake C. Mitchell ◽  
Klaus Gawrisch
Keyword(s):  
Protein Interactions ◽  
Lipid Protein Interactions ◽  
Specific Lipid

scholarly journals Lipid-Protein Interactions of Rhodopsin Investigated by Molecular Dynamics Simulations

2009 ◽  
Vol 96 (3) ◽  
pp. 354a
Author(s):  
Alexander Vogel ◽  
Alan Grossfield ◽  
Michael C. Pitman ◽  
Scott E. Feller ◽  
Michael F. Brown
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Interactions ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations

Molecular simulations and lipid–protein interactions: potassium channels and other membrane proteins

2005 ◽  
Vol 33 (5) ◽  
pp. 916-920 ◽  
Author(s):  
M.S.P. Sansom ◽  
P.J. Bond ◽  
S.S. Deol ◽  
A. Grottesi ◽  
S. Haider ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Binding Site ◽  
Protein Interactions ◽  
Outer Membrane Proteins ◽  
Lipid Binding ◽  
Potassium Channel Kcsa ◽  
Head Groups ◽  
Arginine Residues ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations

Molecular dynamics simulations may be used to probe the interactions of membrane proteins with lipids and with detergents at atomic resolution. Examples of such simulations for ion channels and for bacterial outer membrane proteins are described. Comparison of simulations of KcsA (an α-helical bundle) and OmpA (a β-barrel) reveals the importance of two classes of side chains in stabilizing interactions with the head groups of lipid molecules: (i) tryptophan and tyrosine; and (ii) arginine and lysine. Arginine residues interacting with lipid phosphate groups play an important role in stabilizing the voltage-sensor domain of the KvAP channel within a bilayer. Simulations of the bacterial potassium channel KcsA reveal specific interactions of phosphatidylglycerol with an acidic lipid-binding site at the interface between adjacent protein monomers. A combination of molecular modelling and simulation reveals a potential phosphatidylinositol 4,5-bisphosphate-binding site on the surface of Kir6.2.

Lipid–Protein Interactions in Plasma Membrane Organization and Function

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Taras Sych ◽  
Kandice R. Levental ◽  
Erdinc Sezgin
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Collective Behavior ◽  
Protein Function ◽  
Lipid Binding ◽  
Publication Date ◽  
Membrane Organization ◽  
Lipid Protein Interactions ◽  
And Function ◽  
Specific Lipid

Lipid–protein interactions in cells are involved in various biological processes, including metabolism, trafficking, signaling, host–pathogen interactions, and transmembrane transport. At the plasma membrane, lipid–protein interactions play major roles in membrane organization and function. Several membrane proteins have motifs for specific lipid binding, which modulate protein conformation and consequent function. In addition to such specific lipid–protein interactions, protein function can be regulated by the dynamic, collective behavior of lipids in membranes. Emerging analytical, biochemical, and computational technologies allow us to study the influence of specific lipid–protein interactions, as well as the collective behavior of membranes on protein function. In this article, we review the recent literature on lipid–protein interactions with a specific focus on the current state-of-the-art technologies that enable novel insights into these interactions. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Signal Transduction in the Visual Cascade Involves Specific Lipid-Protein Interactions

2003 ◽  
Vol 278 (25) ◽  
pp. 22853-22860 ◽  
Author(s):  
Elke Hessel ◽  
Martin Heck ◽  
Peter Müller ◽  
Andreas Herrmann ◽  
Klaus Peter Hofmann
Keyword(s):  
Signal Transduction ◽  
Protein Interactions ◽  
Lipid Protein Interactions ◽  
Specific Lipid

scholarly journals Lateral electric field inhibits gel-to-fluid transition in lipid bilayers

2021 ◽  
Author(s):  
Nidhin Thomas ◽  
Ashutosh Agrawal
Keyword(s):  
Electric Field ◽  
Melting Temperature ◽  
Lipid Bilayers ◽  
Electric Fields ◽  
Protein Interactions ◽  
Atomic Scale ◽  
Lateral Electric Field ◽  
Lipid Protein Interactions ◽  
Dynamics Simulations ◽  
Induced Changes

We report evidence of lateral electric field-induced changes in the phase transition temperatures of lipid bilayers. Our atomic scale molecular dynamics simulations show that lateral electric field increases the melting temperature of DPPC, POPC and POPE bilayers. Remarkably, this shift in melting temperature is only induced by lateral electric field, and not normal electric field. This mechanism could provide new mechanistic insights into lipid-lipid and lipid-protein interactions in the presence of endogenous and exogenous electric fields.

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