Actin stabilizing compounds show specific biological effects due to their binding mode

Date

2019-07-05

Author

Wang, Shuaijun
Crevenna, Alvaro H.
Ugur, Ilke
Marıon, Antoıne
Antes, Iris
Kazmaier, Uli
Hoyer, Maria
Lamb, Don C.
Gegenfurtner, Florian
Kliesmetes, Zane
Ziegenhain, Christoph
Enard, Wolfgang
Vollmar, Angelika
Zahler, Stefan

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

158
views

0
downloads

Actin binding compounds are widely used tools in cell biology. We compare the biological and biochemical effects of miuraenamide A and jasplakinolide, a structurally related prototypic actin stabilizer. Though both compounds have similar effects on cytoskeletal morphology and proliferation, they affect migration and transcription in a distinctive manner, as shown by a transcriptome approach in endothelial cells. In vitro, miuraenamide A acts as an actin nucleating, F-actin polymerizing and stabilizing compound, just like described for jasplakinolide. However, in contrast to jasplakinolide, miuraenamide A competes with cofilin, but not gelsolin or Arp2/3 for binding to F-actin. We propose a binding mode of miuraenamide A, explaining both its similarities and its differences to jasplakinolide. Molecular dynamics simulations suggest that the bromophenol group of miurenamide A interacts with residues Tyr133, Tyr143, and Phe352 of actin. This shifts the D-loop of the neighboring actin, creating tighter packing of the monomers, and occluding the binding site of cofilin. Since relatively small changes in the molecular structure give rise to this selectivity, actin binding compounds surprisingly are promising scaffolds for creating actin binders with specific functionality instead of just "stabilizers".

Subject Keywords

Multidisciplinary

URI

https://hdl.handle.net/11511/40137

Journal

SCIENTIFIC REPORTS

DOI

https://doi.org/10.1038/s41598-019-46282-w

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

An embryonic poly(A)-binding protein (ePAB) is expressed in mouse oocytes and early preimplantation embryos. Seli, E; Lalioti, MD; Flaherty, SM; Sakkas, D; Terzi Çizmecioğlu, Nihal; Steitz, JA (Proceedings of the National Academy of Sciences, 2005-01-11) Gene expression during oocyte maturation, fertilization, and early embryo development until zygotic gene activation is regulated mainly by translational activation of maternally derived mRNAs. This process requires the presence of a poly(A)-binding protein. However, the cytoplasmic somatic cell poly(A)-binding protein (PABP1) is not expressed until later in embryogenesis. We recently identified an embryonic poly(A)-binding protein (ePAB) in Xenopus. ePAB is the predominant cytoplasmic PABP in Xenopus oocyte...
Mechanical Fracturing of Core-Shell Undercooled Metal Particles for Heat-Free Soldering Çınar, Simge; Chen, Jiahao; Thuo, Martin (Springer Science and Business Media LLC, 2016-02-23) Phase-change materials, such as meta-stable undercooled (supercooled) liquids, have been widely recognized as a suitable route for complex fabrication and engineering. Despite comprehensive studies on the undercooling phenomenon, little progress has been made in the use of undercooled metals, primarily due to low yields and poor stability. This paper reports the use of an extension of droplet emulsion technique (SLICE) to produce undercooled core-shell particles of structure; metal/oxide shell-acetate ('/'=...
Nanoparticle self-assembly at the interface of liquid crystal droplets Rahimi, Mohammad; Roberts, Tyler F; Armas-Pérez, Julio C; Wang, Xiaoguang; Büküşoğlu, Emre; Abbott, Nicholas L; de Pablo, Juan Jose (Proceedings of the National Academy of Sciences, 2015-04-28) Nanoparticles adsorbed at the interface of nematic liquid crystals are known to form ordered structures whose morphology depends on the orientation of the underlying nematic field. The origin of such structures is believed to result from an interplay between the liquid crystal orientation at the particles' surface, the orientation at the liquid crystal's air interface, and the bulk elasticity of the underlying liquid crystal. In this work, we consider nanoparticle assembly at the interface of nematic drople...
Temporal changes in the gene expression heterogeneity during brain development and aging Isildak, Ulas; Somel, Mehmet; Thornton, Janet M.; Donertas, Handan Melike (Springer Science and Business Media LLC, 2020-03-01) Cells in largely non-mitotic tissues such as the brain are prone to stochastic (epi-)genetic alterations that may cause increased variability between cells and individuals over time. Although increased interindividual heterogeneity in gene expression was previously reported, whether this process starts during development or if it is restricted to the aging period has not yet been studied. The regulatory dynamics and functional significance of putative aging-related heterogeneity are also unknown. Here we ad...
Optical and mechanical properties of fiber-reinforced ceramic matrix optically transparent composites Dericioğlu, Arcan Fehmi (2001-12-01) The idea of increasing the fracture resistance of optically transparent Ceramics by incorporation of continuous fibers with a small expense in their light transmission was applied to a SiC (SCS-6) fiber-reinforced magnesium aluminate spinel matrix composite. It was found that although there is a slight decrease in the light transmittance of the transparent monolithic matrix with increasing fiber volume fraction, a fail-safe mechanism appeared in the composite by the bridging effect of the intact fibers

Citation Formats

S. Wang et al., “Actin stabilizing compounds show specific biological effects due to their binding mode,” SCIENTIFIC REPORTS, pp. 0–0, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/40137.