Intermediate filament structure: the bottom-up approach

Chernyatina, A.A.; Guzenko, Dmytro; Strelkov, S.V.

doi:10.1016/j.ceb.2014.12.007

Cited by 107 publications

(136 citation statements)

References 62 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…This molecular arrangement, which results in looser packing of the α-helices but maintains the overall coiled-coil structure, allows the molecule to wrap continuously around the actin filament, and to adopt different local positions, depending upon its regulatory state (26,27). Distortions from a canonical coiled-coil are common and are often implicated in mediating proteinprotein interactions as observed in intermediate filaments (28). Although several structural examples of stammer/stutters structures have been reported, skip residues have been observed mainly in antiparallel single-chain coiled-coils but there are very few structures for parallel dimeric coiled-coils that include skip residues (29).…”

Section: Discussionmentioning

confidence: 99%

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

Taylor

Buvoli

Korkmaz

et al. 2015

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

View full text Add to dashboard Cite

The rod of sarcomeric myosins directs thick filament assembly and is characterized by the insertion of four skip residues that introduce discontinuities in the coiled-coil heptad repeats. We report here that the regions surrounding the first three skip residues share high structural similarity despite their low sequence homology. Near each of these skip residues, the coiled-coil transitions to a nonclose-packed structure inducing local relaxation of the superhelical pitch. Moreover, molecular dynamics suggest that these distorted regions can assume different conformationally stable states. In contrast, the last skip residue region constitutes a true molecular hinge, providing C-terminal rod flexibility. Assembly of myosin with mutated skip residues in cardiomyocytes shows that the functional importance of each skip residue is associated with rod position and reveals the unique role of the molecular hinge in promoting myosin antiparallel packing. By defining the biophysical properties of the rod, the structures and molecular dynamic calculations presented here provide insight into thick filament formation, and highlight the structural differences occurring between the coiled-coils of myosin and the stereotypical tropomyosin. In addition to extending our knowledge into the conformational and biological properties of coiled-coil discontinuities, the molecular characterization of the four myosin skip residues also provides a guide to modeling the effects of rod mutations causing cardiac and skeletal myopathies.myosin | cardiac/skeletal myopathies | molecular dynamics | coiled-coils | protein structure M uscle contraction is primarily driven by the interactions between actin and myosin and the associated ATP hydrolysis, but the long-range transmission of force is based on the intrinsic ability of both proteins to self-assemble into organized filaments. The myosin thick filament is a well-characterized bipolar structure. The central area, or bare zone, is

show abstract

Section: Discussionmentioning

confidence: 99%

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

Taylor

Buvoli

Korkmaz

et al. 2015

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

View full text Add to dashboard Cite

show abstract

“…Those ␣-helical segments that form coiled coils (coil 1A, coil 1B, and coil 2) are in yellow. The ␣-helical segments that do not form coiled coils are in orange, in particular the pcd and the parallel ␣-helix-forming segments of coil 2, also referred to as pb (13,16). For ease of understanding, we refer to this segment as coil 2A and the remainder of coil 2 as coil 2B in the entire text.…”

Section: Resultsmentioning

confidence: 99%

“…Coil 2 represents a continuous ␣-helix in which the first 35 amino acids form hendecad repeats establishing a right-handed helix with a very large pitch. Hence, in the dimer, the two chains essentially form parallel helices, which are designated as "paired bundle" or pb (16). We refer to this region as coil 2A throughout the text and want to stress that it contains former coil 2A, linker L2, and 11 amino acids of former coil 2B.…”

mentioning

confidence: 99%

“…The remaining segment of coil 2, here referred to as coil 2B, is in heptad configuration, allowing coiled-coil formation, including a "stutter" at position 350 that represents a brief interruption in the heptad pattern by a single hendecad repeat (16). A unique feature of vimentin and sequence-related IF proteins such as desmin and neurofilament proteins is represented by a short segment preceding coil 1A, the pre-coil domain (pcd), which exclusively contains amino acids that are compatible with ␣-helix formation, although no structure has been determined to date (orange box in Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Structural Dynamics of the Vimentin Coiled-coil Contact Regions Involved in Filament Assembly as Revealed by Hydrogen-Deuterium Exchange

Premchandar

Mücke²,

Poznański

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Edited by Norma AllewellIntermediate filaments (IF) are major constituents of the cytoskeleton of metazoan cells. They are not only responsible for the mechanical properties but also for various physiological activities in different cells and tissues. The building blocks of IFs are extended coiled-coil-forming proteins exhibiting a characteristic central ␣-helical domain ("rod"). The fundamental principles of the filament assembly mechanism and the network formation have been widely elucidated for the cytoplasmic IF protein vimentin. Also, a comprehensive structural model for the tetrameric complex of vimentin has been obtained by X-ray crystallography in combination with various biochemical and biophysical techniques. To extend these static data and to investigate the dynamic properties of the full-length proteins in solution during the various assembly steps, we analyzed the patterns of hydrogen-deuterium exchange in vimentin and in four variants carrying point mutations in the IF consensus motifs present at either end of the ␣-helical rod that cause an assembly arrest at the unit-length filament (ULF) stage. The results yielded unique insights into the structural properties of subdomains within the full-length vimentin, in particular in regions of contact in ␣-helical and linker segments that stabilize different oligomeric forms such as tetramers, ULFs, and mature filaments. Moreover, hydrogen-deuterium exchange analysis of the point-mutated variants directly demonstrated the active role of the IF consensus motifs in the oligomerization mechanism of tetramers during ULF formation. Ultimately, using molecular dynamics simulation procedures, we provide a structural model for the subdomain-mediated tetramer/tetramer interaction via "crosscoiling" as the first step of the assembly process. Intermediate filament (IF)3 proteins form highly resilient filaments that are markedly resistant to mechanical stress. Mediated by prominent cytolinker proteins of the plakin family and motor proteins, they integrate actin filaments and microtubules to establish a functional cytoskeleton in metazoan cells and promote optimal tissue function (1). Apart from their basic mechanical function in maintaining cell flexibility, they are also involved in multiple cellular activities that range from cell division and motility to the topological organization of transmembrane channels (2, 3). Because of these multifunctional properties of IF proteins, mutations in IF-encoding genes cause almost 100 different inherited diseases in humans (4, 5). One of the most studied IF proteins, vimentin, forms IFs typical for mesenchymal cells, including endothelial cells, lymphocytes, and the eye lens epithelium (6). Of note, vimentin has long been implicated in many aspects of cancer initiation and progression, including tumorigenesis, epithelial-mesenchymal transition, and the metastatic spread of cancer (7), making this protein an attractive potential target for cancer diagnosis and therapy (8). Therefore, to develop mechanistic insight into the beh...

show abstract

“…Table 1.3 summarises the different types of IFs, together with examples of cells where they are found. Despite the great variability of these IFs, they all share the same secondary structure: a head domain, a rod domain composed of three α helices, and a tail domain [108]. The assembly from monomers to filaments is similar for all the IF proteins, but some specificities exist.…”

Section: Intermediate Filamentsmentioning

confidence: 99%

Investigating Cellular Nanoscale with X-rays

Hémonnot¹

2016

Göttingen Series in X-Ray Physics

View full text Add to dashboard Cite

Intermediate filament structure: the bottom-up approach

Cited by 107 publications

References 62 publications

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

Skip residues modulate the structural properties of the myosin rod and guide thick filament assembly

Structural Dynamics of the Vimentin Coiled-coil Contact Regions Involved in Filament Assembly as Revealed by Hydrogen-Deuterium Exchange

Investigating Cellular Nanoscale with X-rays

Contact Info

Product

Resources

About