Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nature of curvature coupling of amphiphysin with membranes depends on its bound density.

ABSTRACT: Cells are populated by a vast array of membrane-binding proteins that execute critical functions. Functions, like signaling and intracellular transport, require the abilities to bind to highly curved membranes and to trigger membrane deformation. Among these proteins is amphiphysin 1, implicated in clathrin-mediated endocytosis. It contains a Bin-Amphiphysin-Rvs membrane-binding domain with an N-terminal amphipathic helix that senses and generates membrane curvature. However, an understanding of the parameters distinguishing these two functions is missing. By pulling a highly curved nanotube of controlled radius from a giant vesicle in a solution containing amphiphysin, we observed that the action of the protein depends directly on its density on the membrane. At low densities of protein on the nearly flat vesicle, the distribution of proteins and the mechanical effects induced are described by a model based on spontaneous curvature induction. The tube radius and force are modified by protein binding but still depend on membrane tension. In the dilute limit, when practically no proteins were present on the vesicle, no mechanical effects were detected, but strong protein enrichment proportional to curvature was seen on the tube. At high densities, the radius is independent of tension and vesicle protein density, resulting from the formation of a scaffold around the tube. As a consequence, the scaling of the force with tension is modified. For the entire density range, protein was enriched on the tube as compared to the vesicle. Our approach shows that the strength of curvature sensing and mechanical effects on the tube depends on the protein density.

SUBMITTER: Sorre B

PROVIDER: S-EPMC3252917 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Bending stiffness depends on curvature of ternary lipid mixture tubular membranes.

Project description:Lipid and protein sorting and trafficking in intracellular pathways maintain cellular function and contribute to organelle homeostasis. Biophysical aspects of membrane shape coupled to sorting have recently received increasing attention. Here we determine membrane tube bending stiffness through measurements of tube radii, and demonstrate that the stiffness of ternary lipid mixtures depends on membrane curvature for a large range of lipid compositions. This observation indicates amplification by curvature of cooperative lipid demixing. We show that curvature-induced demixing increases upon approaching the critical region of a ternary lipid mixture, with qualitative differences along two roughly orthogonal compositional trajectories. Adapting a thermodynamic theory earlier developed by M. Kozlov, we derive an expression that shows the renormalized bending stiffness of an amphiphile mixture membrane tube in contact with a flat reservoir to be a quadratic function of curvature. In this analytical model, the degree of sorting is determined by the ratio of two thermodynamic derivatives. These derivatives are individually interpreted as a driving force and a resistance to curvature sorting. We experimentally show this ratio to vary with composition, and compare the model to sorting by spontaneous curvature. Our results are likely to be relevant to the molecular sorting of membrane components in vivo.

| S-EPMC2749792 | biostudies-literature

Curvature-undulation coupling as a basis for curvature sensing and generation in bilayer membranes.

Project description:We present coarse-grained molecular dynamics simulations of the epsin N-terminal homology domain interacting with a lipid bilayer and demonstrate a rigorous theoretical formalism and analysis method for computing the induced curvature field in varying concentrations of the protein in the dilute limit. Our theory is based on the description of the height-height undulation spectrum in the presence of a curvature field. We formulated an objective function to compare the acquired undulation spectrum from the simulations to that of the theory. We recover the curvature field parameters by minimizing the objective function even in the limit where the protein-induced membrane curvature is of the same order as the amplitude due to thermal undulations. The coupling between curvature and undulations leads to significant predictions: (i) Under dilute conditions, the proteins can sense a site of spontaneous curvature at distances much larger than their size; (ii) as the density of proteins increases the coupling focuses and stabilizes the curvature field to the site of the proteins; and (iii) the mapping of the protein localization and the induction of a stable curvature is a cooperative process that can be described through a Hill function.

| S-EPMC5024647 | biostudies-literature

Geometric coupling of helicoidal ramps and curvature-inducing proteins in organelle membranes.

Project description:Cellular membranes display an incredibly diverse range of shapes, both in the plasma membrane and at membrane bound organelles. These morphologies are intricately related to cellular functions, enabling and regulating fundamental membrane processes. However, the biophysical mechanisms at the origin of these complex geometries are not fully understood from the standpoint of membrane-protein coupling. In this study, we focused on a minimal model of helicoidal ramps representative of specialized endoplasmic reticulum compartments. Given a helicoidal membrane geometry, we asked what is the distribution of spontaneous curvature required to maintain this shape at mechanical equilibrium? Based on the Helfrich energy of elastic membranes with spontaneous curvature, we derived the shape equation for minimal surfaces, and applied it to helicoids. We showed the existence of switches in the sign of the spontaneous curvature associated with geometric variations of the membrane structures. Furthermore, for a prescribed gradient of spontaneous curvature along the exterior boundaries, we identified configurations of the helicoidal ramps that are confined between two infinitely large energy barriers. Overall our results suggest possible mechanisms for geometric control of helicoidal ramps in membrane organelles based on curvature-inducing proteins.

| S-EPMC6769308 | biostudies-literature

Synergistic insertion of antimicrobial magainin-family peptides in membranes depends on the lipid spontaneous curvature.

Project description:PGLa and magainin 2 (MAG2) are amphiphilic antimicrobial peptides from frog skin with known synergistic activity. The orientation of the two helices in membranes was studied using solid-state (15)N-NMR, for each peptide alone and for a 1:1 mixture of the peptides, in a range of different lipid systems. Two types of orientational behavior emerged. 1), In lipids with negative spontaneous curvature, both peptides remain flat on the membrane surface, when assessed both alone and in a 1:1 mixture. 2), In lipids with positive spontaneous curvature, PGLa alone assumes a tilted orientation but inserts into the bilayer in a transmembrane alignment in the presence of MAG2, whereas MAG2 stays on the surface or gets only slightly tilted, when observed both alone and in the presence of PGLa. The behavior of PGLa alone is identical to that of another antimicrobial peptide, MSI-103, in the same lipid systems, indicating that the curvature-dependent helix orientation is a general feature of membrane-bound peptides and also influences their synergistic intermolecular interactions.

| S-EPMC3602749 | biostudies-literature

Superelasticity of Plasma- and Synthetic Membranes Resulting from Coupling of Membrane Asymmetry, Curvature, and Lipid Sorting.

Project description:Biological cells are contained by a fluid lipid bilayer (plasma membrane, PM) that allows for large deformations, often exceeding 50% of the apparent initial PM area. Isolated lipids self-organize into membranes, but are prone to rupture at small (<2-4%) area strains, which limits progress for synthetic reconstitution of cellular features. Here, it is shown that by preserving PM structure and composition during isolation from cells, vesicles with cell-like elasticity can be obtained. It is found that these plasma membrane vesicles store significant area in the form of nanotubes in their lumen. These act as lipid reservoirs and are recruited by mechanical tension applied to the outer vesicle membrane. Both in experiment and theory, it is shown that a "superelastic" response emerges from the interplay of lipid domains and membrane curvature. This finding allows for bottom-up engineering of synthetic biomaterials that appear one magnitude softer and with threefold larger deformability than conventional lipid vesicles. These results open a path toward designing superelastic synthetic cells possessing the inherent mechanics of biological cells.

| S-EPMC8564416 | biostudies-literature

Bin/Amphiphysin/Rvs (BAR) family members bend membranes in cells.

Project description:We provide direct evidence that Bin/Amphiphysin/Rvs (BAR) family members bend the steady state membrane architecture of organelles in intact cells. In response to inducible BAR molecular actuators, organelles exhibit distinct changes to the orientation and degree of their membrane curvature. This rapidly inducible system may offer a mechanism by which to better understand the structure-function relationship of intracellular organelles.

| S-EPMC4894391 | biostudies-literature

Structural insights into the cooperative remodeling of membranes by amphiphysin/BIN1.

Project description:Amphiphysin2/BIN1 is a crescent-shaped N-BAR protein playing a key role in forming deeply invaginated tubes in muscle T-tubules. Amphiphysin2/BIN1 structurally stabilizes tubular formations in contrast to other N-BAR proteins involved in dynamic membrane scission processes; however, the molecular mechanism of the stabilizing effect is poorly understood. Using cryo-EM, we investigated the assembly of the amphiphysin/BIN1 on a membrane tube. We found that the N-BAR domains self-assemble on the membrane surface in a highly cooperative manner. Our biochemical assays and 3D reconstructions indicate that the N-terminal amphipathic helix H0 plays an important role in the initiation of the tube assembly and further in organizing BAR-mediated polymerization by locking adjacent N-BAR domains. Mutants that lack H0 or the tip portion, which is also involved in interactions of the neighboring BAR unit, lead to a disruption of the polymer organization, even though tubulation can still be observed. The regulatory region of amphiphysin/BIN1 including an SH3 domain does not have any apparent involvement in the polymer lattice. Our study indicates that the H0 helix and the BAR tip are necessary for efficient and organized self-assembly of amphiphysin/N-BAR.

| S-EPMC4614383 | biostudies-literature

?-Synuclein induces both positive mean curvature and negative Gaussian curvature in membranes.

Project description:Using a combination of X-ray scattering, fluorescence correlation spectroscopy, coarse-grained molecular dynamics (MD) simulations and potential of mean force calculations, we have explored the membrane remodeling effects of monomeric ?-synuclein (?S). Our initial findings from multiple approaches are that ?S (1) causes a significant thinning of the bilayer and (2) stabilizes positive mean curvature, such that the maximum principle curvature matches that of synaptic vesicles, ?S-induced tubules, and the synthetic lipid vesicles to which the protein binds most tightly. This suggests that ?S binding to synaptic vesicles likely stabilizes their intrinsic curvature. We then show that ?S induces local negative Gaussian curvature, an effect that occurs in regions of ?S shown previously via NMR and corroborated by MD simulation to have significant conformational flexibility. The induction of negative Gaussian curvature, which has implications for all curvature-sensing and curvature-generating amphipathic ?-helices, supports a hypothesis that connects helix insertion to fusion and fission of vesicles, processes that have recently been linked to ?S function. Then, in an effort to explain these biophysical properties of ?S, we promote an intrinsic curvature-field model that recasts long-range protein-protein interactions in terms of the interactions between the local curvature fields generated by lipid-protein complexes.

| S-EPMC3371389 | biostudies-literature

Roles of amphipathic helices and the bin/amphiphysin/rvs (BAR) domain of endophilin in membrane curvature generation.

Project description:Control of membrane curvature is required in many important cellular processes, including endocytosis and vesicular trafficking. Endophilin is a bin/amphiphysin/rvs (BAR) domain protein that induces vesicle formation by promotion of membrane curvature through membrane binding as a dimer. Using site-directed spin labeling and EPR spectroscopy, we show that the overall BAR domain structure of the rat endophilin A1 dimer determined crystallographically is maintained under predominantly vesiculating conditions. Spin-labeled side chains on the concave surface of the BAR domain do not penetrate into the acyl chain interior, indicating that the BAR domain interacts only peripherally with the surface of a curved bilayer. Using a combination of EPR data and computational refinement, we determined the structure of residues 63-86, a region that is disordered in the crystal structure of rat endophilin A1. Upon membrane binding, residues 63-75 in each subunit of the endophilin dimer form a slightly tilted, amphipathic alpha-helix that directly interacts with the membrane. In their predominant conformation, these helices are located orthogonal to the long axis of the BAR domain. In this conformation, the amphipathic helices are positioned to act as molecular wedges that induce membrane curvature along the concave surface of the BAR domain.

| S-EPMC2888429 | biostudies-literature

Amphiphysin AoRvs167-Mediated Membrane Curvature Facilitates Trap Formation, Endocytosis, and Stress Resistance in <i>Arthrobotrys oligospora</i>.

Project description:Bin1/Amphiphysin/Rvs (BAR) domain-containing proteins mediate fundamental cellular processes, including membrane remodeling and endocytosis. Nematode-trapping (NT) fungi can differentiate to form trapping structures through highly reorganized cell membranes and walls. In this study, we identified the NT fungus Arthrobotrys oligospora ortholog of yeast Rvs167 and documented its involvement in membrane bending and endocytosis. We further confirmed that the deletion of AoRvs167 makes the fungus more hypersensitive to osmotic salt (Nacl), higher temperatures (28 to 30 °C), and the cell wall perturbation agent Congo red. In addition, the disruption of AoRvs167 reduced the trap formation capacity. Hence, AoRvs167 may regulate fungal pathogenicity through the integrity of plasma membranes and cell walls.

| S-EPMC9501185 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data