scholarly journals Haemolytic actinoporins interact with carbohydrates using their lipid-binding module

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160216 ◽  
Author(s):  
Koji Tanaka ◽  
Jose M. M. Caaveiro ◽  
Koldo Morante ◽  
Kouhei Tsumoto
Keyword(s):  
Protein Interactions ◽  
Pore Formation ◽  
Plasma Membranes ◽  
Lipid Binding ◽  
Target Cells ◽  
Sea Anemones ◽  
Molecular Systems ◽  
Membrane Pores ◽  
Living Organisms ◽  
Lipid Protein Interactions

Pore-forming toxins (PFTs) are proteins endowed with metamorphic properties that enable them to stably fold in water solutions as well as in cellular membranes. PFTs produce lytic pores on the plasma membranes of target cells conducive to lesions, playing key roles in the defensive and offensive molecular systems of living organisms. Actinoporins are a family of potent haemolytic toxins produced by sea anemones vigorously studied as a paradigm of α-helical PFTs, in the context of lipid–protein interactions, and in connection with nanopore technologies. We have recently reported that fragaceatoxin C (FraC), an actinoporin, engages biological membranes with a large adhesive motif allowing the simultaneous attachment of up to four lipid molecules prior to pore formation. Since actinoporins also interact with carbohydrates, we sought to understand the molecular and energetic basis of glycan recognition by FraC. By employing structural and biophysical methodologies, we show that FraC engages glycans with low affinity using its lipid-binding module. Contrary to other PFTs requiring separate domains for glycan and lipid recognition, the small single-domain actinoporins economize resources by achieving dual recognition with a single binding module. This mechanism could enhance the recruitment of actinoporins to the surface of target tissues in their marine environment. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

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.

scholarly journals Lipid-mediated Association of the Slg1 Transmembrane Domains in Yeast Plasma Membranes

2021 ◽  
Author(s):  
Azadeh Alavizargar ◽  
Annegret Eltig ◽  
Roland Wedlich Soeldner ◽  
Andreas Heuer
Keyword(s):  
Plasma Membrane ◽  
Protein Interactions ◽  
Plasma Membranes ◽  
Acyl Chain ◽  
Md Simulations ◽  
Receptor Activation ◽  
Transmembrane Domains ◽  
Coarse Grained ◽  
Self Association ◽  
Lipid Protein Interactions

Clustering of transmembrane proteins underlies a multitude of fundamental biological processes at the plasma membrane such as receptor activation, lateral domain formation and mechanotransduction. The self-association of the respective transmembrane domains (TMD) has also been suggested to be responsible for the micron-scaled patterns seen for integral membrane proteins in the budding yeast plasma membrane (PM). However, the underlying interplay between local lipid composition and TMD identity is still not mechanistically understood. In this work we have used coarse-grained molecular dynamics (MD) simulations as well as microscopy experiments (TIRFM) to analyze the behavior of a representative helical yeast TMD (Slg1) within different lipid environments. Via the simulations we evaluated the effect of acyl chain saturation and the presence of anionic lipids head groups on the association of TMDs via simulations. Our simulations revealed that weak lipid-protein interactions significantly affect the configuration of TMD dimers and the free energy of association. Increased amounts of unsaturated phospholipids strongly reduced helix-helix interaction and the presence of phosphatidylserine (PS) lipids only slightly affected the dimer. Experimentally, the network factor, characterizing the association strength on a mesoscopic level, was measured in the presence and absence of PS lipids. Consistently with the simulations, no significant effect was observed. We also found that formation of TMD dimers in turn increased the order parameter of the surrounding lipids and induced long-range perturbations in lipid organization, shedding new light on the lipid-mediated dimerization of TMDs in complex lipid mixtures.

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 The Membrane Proximal Domain of TRPV1 and TRPV2 Channels Mediates Protein–Protein Interactions and Lipid Binding In Vitro

2019 ◽  
Vol 20 (3) ◽  
pp. 682 ◽  
Author(s):  
Pau Doñate-Macián ◽  
Elena Álvarez-Marimon ◽  
Francesc Sepulcre ◽  
José Vázquez-Ibar ◽  
Alex Perálvarez-Marín
Keyword(s):  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Lipid Binding ◽  
Transient Receptor Potential Channels ◽  
Trpv Channels ◽  
Potential Channels ◽  
Transient Receptor ◽  
Lipid Protein Interactions

Constitutive or regulated membrane protein trafficking is a key cell biology process. Transient receptor potential channels are somatosensory proteins in charge of detecting several physical and chemical stimuli, thus requiring fine vesicular trafficking. The membrane proximal or pre-S1 domain (MPD) is a highly conserved domain in transient receptor potential channels from the vanilloid (TRPV) subfamily. MPD shows traits corresponding to protein-protein and lipid-protein interactions, and protein regulatory regions. We have expressed MPD of TRPV1 and TRPV2 as green fluorescente protein (GFP)-fusion proteins to perform an in vitro biochemical and biophysical characterization. Pull-down experiments indicate that MPD recognizes and binds Soluble N-ethylmaleimide-sensitive factor Attachment Protein Receptors (SNARE). Synchrotron radiation scattering experiments show that this domain does not self-oligomerize. MPD interacts with phosphatidic acid (PA), a metabolite of the phospholipase D (PLD) pathway, in a specific manner as shown by lipid strips and Trp fluorescence quenching experiments. We show for the first time, to the best of our knowledge, the binding to PA of an N-terminus domain in TRPV channels. The presence of a PA binding domain in TRPV channels argues for putative PLD regulation. Findings in this study open new perspectives to understand the regulated and constitutive trafficking of TRPV channels exerted by protein-protein and lipid-protein interactions.

scholarly journals Molecular mechanism of pore formation by aerolysin-like proteins

2017 ◽  
Vol 372 (1726) ◽  
pp. 20160209 ◽  
Author(s):  
Marjetka Podobnik ◽  
Matic Kisovec ◽  
Gregor Anderluh
Keyword(s):  
Cell Biology ◽  
Pore Formation ◽  
Target Cells ◽  
Membrane Pores ◽  
Surface Molecules ◽  
Structural Details ◽  
Transmembrane Pores ◽  
Future Drug ◽  
Pore Forming Proteins ◽  
Unique Domain

Aerolysin-like pore-forming proteins are an important family of proteins able to efficiently damage membranes of target cells by forming transmembrane pores. They are characterized by a unique domain organization and mechanism of action that involves extensive conformational rearrangements. Although structures of soluble forms of many different members of this family are well understood, the structures of pores and their mechanism of assembly have been described only recently. The pores are characterized by well-defined β-barrels, which are devoid of any vestibular regions commonly found in other protein pores. Many members of this family are bacterial toxins; therefore, structural details of their transmembrane pores, as well as the mechanism of pore formation, are an important base for future drug design. Stability of pores and other properties, such as specificity for some cell surface molecules, make this family of proteins a useful set of molecular tools for molecular recognition and sensing in cell biology. This article is part of the themed issue ‘Membrane pores: from structure and assembly, to medicine and technology’.

scholarly journals Influence of phosphatidylserine on (Na+ + K+)-stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes

1984 ◽  
Vol 220 (1) ◽  
pp. 301-307 ◽  
Author(s):  
S Tsakiris ◽  
G Deliconstantinos
Keyword(s):  
Protein Interactions ◽  
Plasma Membranes ◽  
Physiological Processes ◽  
Maximal Stimulation ◽  
Dog Brain ◽  
The Central Nervous System ◽  
Hill Coefficients ◽  
Lipid Protein Interactions ◽  
Synaptosomal Plasma Membranes ◽  
Allosteric Properties

Phosphatidylserine (PtdSer) incubated with synaptosomal plasma membranes (SPM) of dog brain is incorporated into SPM in proportion to its concentration in the incubation medium. Low PtdSer concentrations progressively activated the SPM-associated (Na+ + K+)-stimulated ATPase and acetylcholinesterase. Increasing the PtdSer concentration above that which maximally stimulated the enzyme activities effected a progressive inhibition with respect to maximal stimulation. Arrhenius plots of (Na+ + K+ + Mg2+)-dependent ATPase and 5′-nucleotidase revealed a clear break at 23-24 degrees C for both enzymes in SPM untreated with PtdSer (controls), whereas a linear relation was obtained for SPM treated with PtdSer. Changes in the allosteric properties of (Na+ + K+)-stimulated ATPase by fluoride (F-) and/or of 5′-nucleotidase by concanavalin A (i.e. changes of Hill coefficients) indicate that PtdSer increases the membrane fluidity. These results suggest that modifications of lipid-protein interactions in SPM induced by PtdSer may have implications in the physiological processes in the central nervous system.

scholarly journals Lipid–protein interactions in plasma membranes of fiber cells isolated from the human eye lens

2014 ◽  
Vol 120 ◽  
pp. 138-151 ◽  
Author(s):  
Marija Raguz ◽  
Laxman Mainali ◽  
William J. O'Brien ◽  
Witold K. Subczynski
Keyword(s):  
Protein Interactions ◽  
Plasma Membranes ◽  
Eye Lens ◽  
Fiber Cells ◽  
Human Eye ◽  
Lipid Protein Interactions

scholarly journals Model Membrane Systems Used to Study Plasma Membrane Lipid Asymmetry

Symmetry ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1356
Author(s):  
Haden L. Scott ◽  
Kristen B. Kennison ◽  
Thais A. Enoki ◽  
Milka Doktorova ◽  
Jacob J. Kinnun ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Plasma Membranes ◽  
Membrane Lipid ◽  
Model Membrane ◽  
Model Membranes ◽  
Computational Techniques ◽  
Symmetric Model ◽  
Membrane Asymmetry ◽  
Asymmetric Model ◽  
Lipid Protein Interactions

It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid–lipid and lipid–protein interactions. This is primarily due to the difficulty in preparing stable, asymmetric model membranes that are amenable to biophysical studies. However, in the last 20 years, efforts have been made in producing more biologically faithful model membranes. Here, we review several recently developed experimental and computational techniques for the robust generation of asymmetric model membranes and highlight a new and particularly promising technique to study membrane asymmetry.

Sign in / Sign up

Export Citation Format

Share Document