Myopathy-Sensitive G-Actin Segment 227-235 Is Involved in Salt-Induced Stabilization of Contacts within the Actin Filament
| Autor: | Andrzej A. Kasprzak, Piotr Dobryszycki, Joanna Gruszczynska-Biegala, Sofia Khaitlina, Hanna Strzelecka-Gołaszewska, Andrzej Stefan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Conformational change Cation binding salt-induced stabilization Protein subunit Magnesium Chloride macromolecular substances Catalysis Article Segment 227-235 Inorganic Chemistry Protein filament lcsh:Chemistry 03 medical and health sciences C-terminus 0302 clinical medicine Muscular Diseases actin proteolysis Animals Physical and Theoretical Chemistry Molecular Biology lcsh:QH301-705.5 actin-associated myopathy Spectroscopy Actin Chemistry Organic Chemistry Subtilisin General Medicine Actins Computer Science Applications Actin Cytoskeleton 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Ionic strength actin filaments Biophysics subtilisin Rabbits 030217 neurology & neurosurgery Copper |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, Vol 22, Iss 2327, p 2327 (2021) |
| ISSN: | 1422-0067 |
| Popis: | Formation of stable actin filaments, critically important for actin functions, is determined by the ionic strength of the solution. However, not much is known about the elements of the actin fold involved in ionic-strength-dependent filament stabilization. In this work, F-actin was destabilized by Cu2+ binding to Cys374, and the effects of solvent conditions on the dynamic properties of F-actin were correlated with the involvement of Segment 227-235 in filament stabilization. The results of our work show that the presence of Mg2+ at the high-affinity cation binding site of Cu-modified actin polymerized with MgCl2 strongly enhances the rate of filament subunit exchange and promotes the filament instability. In the presence of 0.1 M KCl, the filament subunit exchange was 2–3-fold lower than that in the MgCl2-polymerized F-actin. This effect correlates with the reduced accessibility of the D-loop and Segment 227-235 on opposite filament strands, consistent with an ionic-strength-dependent conformational change that modulates involvement of Segment 227-235 in stabilization of the intermonomer interface. KCl may restrict the mobility of the α-helix encompassing part of Segment 227-235 and/or be bound to Asp236 at the boundary of Segment 227-235. These results provide experimental evidence for the involvement of Segment 227-235 in salt-induced stabilization of contacts within the actin filament and suggest that they can be weakened by mutations characteristic of actin-associated myopathies. |
| Databáze: | OpenAIRE |
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