Vimentin Coil 1A—A Molecular Switch Involved in the Initiation of Filament Elongation

Meier, Markus; Padilla, G. Pauline; Herrmann, Harald; Wedig, Tatjana; Hergt, Michaela; Patel, Trushar R.; Stetefeld, Jörg; Aebi, Ueli; Burkhard, Peter

doi:10.1016/j.jmb.2009.04.067

Cited by 96 publications

(134 citation statements)

References 71 publications

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“…1A). This very pattern is found in the crystal structure of coil-1A (Y117L mutant) dimer [PDB entry 3G1E (27)]. In vimentin, the interruption of α-helical structure at linker L1 is predicted for eight residues, Gly140 to Gly147 (Fig.…”

Section: Resultsmentioning

confidence: 61%

“…3A). However, the arrangement of the 1A parts within the 1ABL structure is radically different from a parallel CC dimer, even though such a dimer should be very stable and indeed is found in the crystals of the 1A (Y117L) fragment (27). Instead, a tetrameric left-handed CC assembly involving 1A helices from crystal symmetry-related molecules is found.…”

Section: Resultsmentioning

confidence: 92%

“…Mutation. Since the coil-1A and linker-L1 regions remained unresolved in the crystal structure of the 1AB fragment, we have prepared a point-mutated variant (termed 1ABL) which carries the Y117L mutation known to radically stabilize the CC formation within coil 1A (27). The obtained 1ABL crystals diffracted to 2.45 Å resolution and had very different space group and cell parameters than the 1AB crystals (Table S1).…”

Section: Resultsmentioning

confidence: 99%

“…The coil-1A fragment of vimentin was present as a monomer in crystals (18), and it exhibited only a weak CC-forming capacity, as manifested by its low thermal stability (melting temperature T m ¼ 32°C at 1 mg∕ml concentration) (27). However, the CC formation within this fragment can be drastically stabilized by a point mutation Y117L (leading to T m ¼ 71°C) (27), which replaces the bulky Tyr side chain in a core CC position (d) by a favorable Leu residue. Moreover, the full-length vimentin Y117L mutant does not assemble beyond the ULF stage both in vitro and in cDNA-transfected cultured cells (27,33).…”

Section: Discussionmentioning

confidence: 99%

“…However, the CC formation within this fragment can be drastically stabilized by a point mutation Y117L (leading to T m ¼ 71°C) (27), which replaces the bulky Tyr side chain in a core CC position (d) by a favorable Leu residue. Moreover, the full-length vimentin Y117L mutant does not assemble beyond the ULF stage both in vitro and in cDNA-transfected cultured cells (27,33). These observations led to suggest that coil 1A may serve as a dynamic "switch" with the functionally significant property to alternate between a monomeric helix and a CC dimer depending on the particular IF assembly stage (27,34).…”

Section: Discussionmentioning

confidence: 99%

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Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly

Chernyatina

Nicolet

Aebi

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Together with actin filaments and microtubules, intermediate filaments (IFs) are the basic cytoskeletal components of metazoan cells. Over 80 human diseases have been linked to mutations in various IF proteins to date. However, the filament structure is far from being resolved at the atomic level, which hampers rational understanding of IF pathologies. The elementary building block of all IF proteins is a dimer consisting of an α-helical coiled-coil (CC) "rod" domain flanked by the flexible head and tail domains. Here we present three crystal structures of overlapping human vimentin fragments that comprise the first half of its rod domain. Given the previously solved fragments, a nearly complete atomic structure of the vimentin rod has become available. It consists of three α-helical segments (coils 1A, 1B, and 2) interconnected by linkers (L1 and L12). Most of the CC structure has a left-handed twist with heptad repeats, but both coil 1B and coil 2 also exhibit untwisted, parallel stretches with hendecad repeats. In the crystal structure, linker L1 was found to be α-helical without being involved in the CC formation. The available data allow us to construct an atomic model of the antiparallel tetramer representing the second level of vimentin assembly. Although the presence of the nonhelical head domains is essential for proper tetramer stabilization, the precise alignment of the dimers forming the tetramer appears to depend on the complementarity of their surface charge distribution patterns, while the structural plasticity of linker L1 and coil 1A plays a role in the subsequent IF assembly process.X-ray crystallography | cytoskeleton | coiled coil

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Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly

Chernyatina

Nicolet

Aebi

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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154

164

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Abiotic Stress Response in Plants: Role of Cytoskeleton

Soda

Singla‐Pareek

Pareek

2016

Abiotic Stress Response in Plants

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Tension Causes Unfolding of Intracellular Vimentin Intermediate Filaments

et al. 2020

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and intermediate filaments (IFs). While the roles of actin-based networks and MT in cell mechanics and cell function have been extensively studied (reviewed, e.g., in refs. [2, 3]), the contribution of IFs to cell mechanics is still relatively opaque, beyond their function in bearing large tensile forces. Of the cytoskeletal proteins, IF constituent proteins have the unique feature of being able to undergo molecular structural changes in response to external loads, at least in vitro, as shown by single-molecule experiments and molecular dynamics simulations. [4-7] This structural polymorphism observed outside of a cellular context has led to the hypothesis that IFs could play a role in intracellular mechanotransduction-relaying information about the cell's mechanical state into biochemical changes that influence cell shape [8-10] and phenotype. [11] IF proteins consist dimeric building blocks ≈45 nm in length that assemble into ≈60 nm antiparallel tetrameters (due to dimer overlap), which laterally associate into unit length filaments that assemble longitudinally to make apolar filaments. These filaments can further bundle into fibers and form networks. [7,12,13] Crystal structures show that IF protein are at least 67% α-helical. [14,15] Individual IFs self-assemble into quite diverse networks with location-specific architectures and composition in cells. [8] IFs proteins can form both ionic and hydrophobic molecular contacts resulting in multiple stabilizing interactions. In addition, proteins such as plectin help bundling and cross-bridging between IFs and to stress fibers and MT. [8,16] Vimentin is one IF protein that forms cytoplasmic IF networks and is particularly interesting because of its important role in cell adhesion, mechanical stability, [17-19] and cell migration, as well as intracellular signaling. [8,20] Specific demonstrations of laser ablation of super-stretched cells showed that the IF network is load bearing; however, this effect was not observed on relaxed cells grown on very soft substrates. [21] Moreover, vimentin has been established as a marker of the epithelial-to-mesenchymal transitions (EMT) in embryogenesis and in tumor metastasis, as the cytoplasmic IF network in epithelial cells mostly consists of keratin that is converted to a vimentin-rich IF network during EMT. [10,22-24] A complex multi-regime response of IF protein structure to deformation has been revealed via computational [7,25,26] and in vitro experimental [4,5] studies of IF protein mechanics.

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Vimentin Coil 1A—A Molecular Switch Involved in the Initiation of Filament Elongation

Cited by 96 publications

References 71 publications

Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly

Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly

Abiotic Stress Response in Plants: Role of Cytoskeleton

Tension Causes Unfolding of Intracellular Vimentin Intermediate Filaments

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