Intrinsically disordered proteins drive membrane curvature

Busch, David J.; Houser, Justin R.; Hayden, Carl C.; Sherman, Michael B; Lafer, Eileen M.; Stachowiak, Jeanne C.

doi:10.1038/ncomms8875

Cited by 241 publications

(240 citation statements)

References 62 publications

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“…Based on their structures, these proteins are expected to occupy increasing areas on the membrane surface: ubiquitin (5 nm 2 ), ENTH (16 nm 2 ), TfR (70 nm 2 ). We have previously used the data on ENTH as a standard of comparison to large intrinsically disordered proteins 19 . We began by measuring the diffusion time of each membrane bound protein under dilute conditions as well as the diffusivity of the labeled membrane tag, 6-histidine, alone, Fig.…”

Section: Resultsmentioning

confidence: 99%

The impact of physiological crowding on the diffusivity of membrane bound proteins

et al. 2016

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Diffusion of transmembrane and peripheral membrane-bound proteins within the crowded cellular membrane environment is essential to diverse biological processes including cellular signaling, endocytosis, and motility. Nonetheless we presently lack a detailed understanding of the influence of physiological levels of crowding on membrane protein diffusion. Utilizing quantitative in vitro measurements, here we demonstrate that the diffusivities of membrane bound proteins follow a single linearly decreasing trend with increasing membrane coverage by proteins. This trend holds for homogenous protein populations across a range of protein size and for heterogeneous mixtures of proteins of different sizes, such that protein diffusivity is controlled by the total coverage of the surrounding membrane. These results demonstrate that steric exclusion within the crowded membrane environment can fundamentally limit the diffusive rate of proteins, regardless of their size. In cells this “speed limit” could be modulated by changes in local membrane coverage, providing a mechanism for tuning the rate of molecular interaction and assembly.

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Section: Resultsmentioning

confidence: 99%

The impact of physiological crowding on the diffusivity of membrane bound proteins

et al. 2016

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“…Briefly, membrane curvature necessary for vesicular formation is facilitated by hydrophobic mismatch as results of protein crowding, as well as scaffolding mechanisms with the aid of coat proteins [36*]. Hydrophobic mismatch causes proteins, which have large extramembrane components diffusing in the membrane, to induce molecular crowding in order to lower the accessible membrane surface area and reduced lipids [37]. …”

Section: Interplay Between Lipids and Proteins In Vesicular Formationmentioning

confidence: 99%

Membrane lipids and cell signaling

Sunshine

Iruela‐Arispe

2017

Current Opinion in Lipidology

195

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Purpose of review Reception and transmission of signals across the plasma membrane has been a function generally attributed to transmembrane proteins. In the last three years, however, a growing number of reports have further acknowledged important contributions played by membrane lipids in the process of signal transduction. Recent findings In particular, the constituency of membrane lipids can regulate how proteins with SH2 domains and molecules like K-Ras expose their catalytic domains to the cytosol and interact with effectors and second messengers. Recent reports have also shown that the degree of saturation of phospholipids can reduce the activation of certain G-protein coupled receptors, as well as signaling downstream to Toll-like receptor 4 with consequences to NFkB activation and inflammation. Levels of specific gangliosides in the membrane were reported to activate integrins in a cell-autonomous manner affecting tumor cell migration. Furthermore, high resolution of the association of cholesterol with the Smoothened receptor has clarified its participation in sonic hedgehog signaling. These are some of the key advancements that have further propelled our understanding of the broad versatile contributions of membrane lipids in signal transduction. Summary As we gain definitive detail regarding the impact of lipid-protein interactions and their consequences to cell function, the options for therapeutic targeting expand with the possibility of greater specificity.

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“…Furthermore, the formation of necks is a critical step in the interaction of toxins and viral fusion proteins with cellular membranes [6][7][8][9] . These structures are also observed in synthetic membrane systems such as in giant unilamellar vesicles subject to osmotic stress [10][11][12] , lipid heterogeneities 13,14 , protein insertion or crowding 15,16 , and membrane-substrate interactions 17 . As shown in Fig.…”

Section: Introductionmentioning

confidence: 97%

Gaussian curvature directs the distribution of spontaneous curvature on bilayer membrane necks

Chabanon

Rangamani

2018

Soft Matter

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Formation of membrane necks is crucial for fission and fusion in lipid bilayers. In this work, we seek to answer the following fundamental question: what is the relationship between protein-induced spontaneous mean curvature and the Gaussian curvature at a membrane neck? Using an augmented Helfrich model for lipid bilayers to include membrane-protein interaction, we solve the shape equation on catenoids to find the field of spontaneous curvature that satisfies mechanical equilibrium of membrane necks. In this case, the shape equation reduces to a variable coefficient Helmholtz equation for spontaneous curvature, where the source term is proportional to the Gaussian curvature. We show how this latter quantity is responsible for non-uniform distribution of spontaneous curvature in minimal surfaces. We then explore the energetics of catenoids with different spontaneous curvature boundary conditions and geometric asymmetries to show how heterogeneities in spontaneous curvature distribution can couple with Gaussian curvature to result in membrane necks of different geometries.

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Intrinsically disordered proteins drive membrane curvature

Cited by 241 publications

References 62 publications

The impact of physiological crowding on the diffusivity of membrane bound proteins

The impact of physiological crowding on the diffusivity of membrane bound proteins

Membrane lipids and cell signaling

Gaussian curvature directs the distribution of spontaneous curvature on bilayer membrane necks

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