Formins Regulate Actin Filament Flexibility through Long Range Allosteric Interactions

The high-level organization of the cell is embedded in long-range interactions that connect distinct cellular processes. Existing approaches for detecting long-range interactions consist of propagating information from source nodes through cellular networks, but the selection of source nodes is inherently biased by prior knowledge. Here, we sought to derive an unbiased view of long-range interactions by adapting a perturbation-response scanning strategy initially developed for identifying allosteric interactions within proteins. We deployed this strategy onto an elastic network model of the yeast genetic network. The genetic network revealed a superior propensity for long-range interactions relative to simulated networks with similar topology. Long-range interactions were detected systematically throughout the network and found to be enriched in specific biological processes. Furthermore, perturbation-response scanning identified the major sources and receivers of information in the network, named effector and sensor genes, respectively. Effectors formed dense clusters centrally integrated into the network, whereas sensors formed loosely connected antenna-shaped clusters. Long-range interactions between effector and sensor clusters represent the major paths of information in the network. Our results demonstrate that elastic network modeling of cellular networks constitutes a promising strategy to probe the high-level organization of the cell.

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Toward an alignment of the actin molecule within the actin filament

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075981 ◽

1983 ◽

Vol 41 ◽

pp. 450-451

Author(s):

P.R. Smith ◽

W.E. Fowler ◽

U. Aebi

Keyword(s):

Actin Filament ◽

Diffraction Data ◽

Quantitative Estimate ◽

Molecular Model ◽

Quantitative Comparison ◽

Regulatory Proteins ◽

Essential Information ◽

X Ray ◽

Maximum Resolution ◽

Lack Of Information

An understanding of the specific interactions of actin with regulatory proteins has been limited by the lack of information about the structure of the actin filament. Molecular actin has been studied in actin-DNase I complexes by single crystal X-ray analysis, to a resolution of about 0.6nm, and in the electron microscope where two dimensional actin sheets have been reconstructed to a maximum resolution of 1.5nm. While these studies have shown something of the structure of individual actin molecules, essential information about the orientation of actin in the filament is still unavailable.The work of Egelman & DeRosier has, however, suggested a method which could be used to provide an initial quantitative estimate of the orientation of actin within the filament. This method involves the quantitative comparison of computed diffraction data from single actin filaments with diffraction data derived from synthetic filaments constructed using the molecular model of actin as a building block. Their preliminary work was conducted using a model consisting of two juxtaposed spheres of equal size.

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The 3-Dimensional Molecular Structure of the Actin Filament Revisited

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119223 ◽

1985 ◽

Vol 43 ◽

pp. 480-481

Author(s):

U. Aebi ◽

R. Millonig ◽

H. Salvo

Keyword(s):

Actin Filament ◽

Supramolecular Assembly ◽

Specimen Preparation ◽

X Ray Diffraction ◽

Single Filament ◽

X Ray ◽

3 Dimensional ◽

Filament Diameter ◽

Preparation Conditions ◽

Apparent Diameter

To date, most 3-D reconstructions of undecorated actin filaments have been obtained from actin filament paracrystal data (for refs, see 1,2). However, due to the fact that (a) the paracrystals may be several filament layers thick, and (b) adjacent filaments may sustantially interdigitate, these reconstructions may be subject to significant artifacts. None of these reconstructions has permitted unambiguous tracing or orientation of the actin subunits within the filament. Furthermore, measured values for the maximal filament diameter both determined by EM and by X-ray diffraction analysis, vary between 6 and 10 nm. Obviously, the apparent diameter of the actin filament revealed in the EM will critically depend on specimen preparation, since it is a rather flexible supramolecular assembly which can easily be bent or distorted. To resolve some of these ambiguities, we have explored specimen preparation conditions which may preserve single filaments sufficiently straight and helically ordered to be suitable for single filament 3-D reconstructions, possibly revealing molecular detail.

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