When Physics Takes Over: BAR Proteins and Membrane Curvature

Šimunović, Mijo; Voth, Gregory A.; Callan-Jones, Andrew; Bassereau, Patricia

doi:10.1016/j.tcb.2015.09.005

Cited by 256 publications

(258 citation statements)

References 62 publications

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“…In the latter mechanism, the protein domain has a strong affinity for the lipid polar head groups and adsorbs onto the lipid membrane. A BAR (Bin/Amphiphysin/Rvs) domain, which consists of a banana-shaped dimer, mainly bends the membrane along the domain axis via scaffolding [7][8][9][10][11]. Some of the BAR superfamily proteins, such as N-BAR proteins, also have hydrophobic insertions.…”

Section: Introductionmentioning

confidence: 99%

Membrane structure formation induced by two types of banana-shaped proteins

Noguchi

Fournier

2017

Soft Matter

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The assembly of banana-shaped rodlike proteins on membranes, and the associated membrane shape transformations, are investigated by analytical theory and coarse-grained simulations. The membrane-mediated interactions between two banana-shaped inclusions are derived theoretically using a point-like formalism based on fixed anisotropic curvatures, both for zero surface tension and for finite surface tension. On a larger scale, the interactions between assemblies of such rodlike inclusions are determined analytically. Meshless membrane simulations are performed in the presence of a large number of inclusions of two types, corresponding to curved rods of opposite curvatures, both for flat membranes and vesicles. Rods of the same type aggregate into linear assemblies perpendicular to the rod axis, leading to membrane tubulation. However, rods of the other type, those of opposite curvature, are attracted to the lateral sides of these assemblies, and stabilize a straight bump structure that prevents tubulation. When the two types of rods have almost opposite curvatures, the bumps attract one another, forming a stripe structure. Positive surface tension is found to stabilize the stripe formation. The simulation results agree well with the theoretical predictions provided the point-like curvatures of the model are scaled-down to account for the effective flexibility of the simulated rods.

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Section: Introductionmentioning

confidence: 99%

Membrane structure formation induced by two types of banana-shaped proteins

Noguchi

Fournier

2017

Soft Matter

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“…Some of the BAR superfamily proteins, such as N-BAR proteins, also have hydrophobic insertions. Experimentally, the formation of membrane tubes and curvature-sensing by various types of BAR superfamily proteins have been observed [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Dysfunctional BAR proteins are considered to be implicated in neurodegenerative, cardiovascular, and neoplastic diseases.…”

Section: Introductionmentioning

confidence: 99%

Shape deformation of lipid membranes by banana-shaped protein rods: Comparison with isotropic inclusions and membrane rupture

Noguchi

2016

Phys. Rev. E

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The assembly of curved protein rods on fluid membranes is studied using implicit-solvent meshless membrane simulations. As the rod curvature increases, the rods on a membrane tube assemble along the azimuthal direction first and subsequently along the longitudinal direction. Here, we show that both transition curvatures decrease with increasing rod stiffness. For comparison, curvature-inducing isotropic inclusions are also simulated. When the isotropic inclusions have the same bending rigidity as the other membrane regions, the inclusions are uniformly distributed on the membrane tubes and vesicles even for large spontaneous curvature of the inclusions. However, the isotropic inclusions with much larger bending rigidity induce shape deformation and are concentrated on the region of a preferred curvature. For high rod density, high rod stiffness, and/or low line tension of the membrane edge, the rod assembly induces vesicle rupture, resulting in the formation of a high-genus vesicle. A gradual change in the curvature suppresses this rupture. Hence, large stress, compared to the edge tension, induced by the rod assembly is the key factor determining rupture. For rod curvature with the opposite sign to the vesicle curvature, membrane rupture induces inversion of the membrane, leading to division into multiple vesicles as well as formation of a high-genus vesicle.

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“…Additionally, BAR proteins can associate into highly ordered assemblies on the membrane, thus collectively altering its shape and mechanics (7)(8)(9)(10). Precisely how they assemble and affect the membrane is argued to depend on the surface density of proteins, membrane tension, and membrane shape (11). On a flat membrane at a low surface density, BAR proteins can form strings and a meshlike network, which can give rise to budding and tubulation (12)(13)(14)(15)(16).…”

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confidence: 99%

How curvature-generating proteins build scaffolds on membrane nanotubes

Šimunović

Evergren

Golushko

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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128

112

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Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube's length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30-40% of a tube's surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes.protein scaffold | BAR proteins | membrane curvature | self-assembly | endocytosis

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When Physics Takes Over: BAR Proteins and Membrane Curvature

Cited by 256 publications

References 62 publications

Membrane structure formation induced by two types of banana-shaped proteins

Membrane structure formation induced by two types of banana-shaped proteins

Shape deformation of lipid membranes by banana-shaped protein rods: Comparison with isotropic inclusions and membrane rupture

How curvature-generating proteins build scaffolds on membrane nanotubes

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