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Molecular structure of soluble vimentin tetramers
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SYSNO ASEP 0576106 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Molecular structure of soluble vimentin tetramers Author(s) Vermeire, P. (BE)
Lilina, A. V. (BE)
Hashim, H.M. (BE)
Dlabolova, Lada (MBU-M)
Fiala, Jan (MBU-M) ORCID, RID
Beelen, S. (BE)
Kukačka, Zdeněk (MBU-M) RID, ORCID
Harvey, J. N. (BE)
Novák, Petr (MBU-M) RID, ORCID
Strelkov, S. V. (BE)Article number 8841 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 13, č. 1 (2023)Number of pages 16 s. Language eng - English Country US - United States Keywords intermediate-filament structure ; architecture ; scattering ; rod ; proteins ; segment ; lamin ; 1a ; units1a OECD category Biochemistry and molecular biology R&D Projects GA22-27695S GA ČR - Czech Science Foundation (CSF) Research Infrastructure CIISB II - 90127 - Masarykova univerzita Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 001001303600057 EID SCOPUS 85160704062 DOI 10.1038/s41598-023-34814-4 Annotation Intermediate filaments (IFs) are essential constituents of the metazoan cytoskeleton. A vast family of cytoplasmic IF proteins are capable of self-assembly from soluble tetrameric species into typical 10-12 nm wide filaments. The primary structure of these proteins includes the signature central 'rod' domain of similar to 300 residues which forms a dimeric alpha-helical coiled coil composed of three segments (coil1A, coil1B and coil2) interconnected by non-helical, flexible linkers (L1 and L12). The rod is flanked by flexible terminal head and tail domains. At present, the molecular architecture of mature IFs is only poorly known, limiting our capacity to rationalize the effect of numerous disease-related mutations found in IF proteins. Here we addressed the molecular structure of soluble vimentin tetramers which are formed by two antiparallel, staggered dimers with coil1B domains aligned (A(11) tetramers). By examining a series of progressive truncations, we show that the presence of the coil1A domain is essential for the tetramer formation. In addition, we employed a novel chemical cross-linking pipeline including isotope labelling to identify intra- and interdimeric cross-links within the tetramer. We conclude that the tetramer is synergistically stabilized by the interactions of the aligned coil1B domains, the interactions between coil1A and the N-terminal portion of coil2, and the electrostatic attraction between the oppositely charged head and rod domains. Our cross-linking data indicate that, starting with a straight A(11) tetramer, flexibility of linkers L1 and L12 enables 'backfolding' of both the coil1A and coil2 domains onto the tetrameric core formed by the coil1B domains. Through additional small-angle X-ray scattering experiments we show that the elongated A(11) tetramers dominate in low ionic strength solutions, while there is also a significant structural flexibility especially in the terminal domains. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2024 Electronic address https://www.nature.com/articles/s41598-023-34814-4
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