Towards a molecular description of intermediate filament structure and assembly

• Published in: Experimental cell research Vol. 313; no. 10; pp. 2204 - 2216
• Main Authors: Parry, David A.D., Strelkov, Sergei V., Burkhard, Peter, Aebi, Ueli, Herrmann, Harald
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.06.2007; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Assembly; Cellular biology; Cryoelectron Microscopy - methods; CRYSTALLIZATION; CRYSTALLOGRAPHY; Crystallography, X-Ray - methods; DIMERS; ELECTRON MICROSCOPY; EPIDERMIS; Humans; Intermediate Filament Proteins - chemistry; Intermediate Filament Proteins - metabolism; Intermediate Filament Proteins - ultrastructure; Intermediate filaments; Intermediate Filaments - chemistry; Intermediate Filaments - metabolism; Intermediate Filaments - ultrastructure; KERATIN; Models, Molecular; Molecular biology; Polymorphism; Protein Structure, Tertiary - physiology; Proteins; Scattering, Small Angle; SMALL ANGLE SCATTERING; Small-angle X-ray scattering; TOMOGRAPHY; Vimentin; Vimentin - chemistry; Vimentin - metabolism; Vimentin - ultrastructure; X RADIATION; X-RAY DIFFRACTION; Vimentin; Keratin; Intermediate filaments; EM; MPL; IF; ULF; Assembly; SAXS; STEM; Polymorphism; Small-angle X-ray scattering
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2007.04.009

Intermediate filaments (IFs) represent one of the prominent cytoskeletal elements of metazoan cells. Their constituent proteins are coded by a multigene family, whose members are expressed in complex patterns that are controlled by developmental programs of differentiation. Hence, IF proteins found in epidermis differ significantly from those in muscle or neuronal tissues. Due to their fibrous nature, which stems from a fairly conserved central α-helical coiled-coil rod domain, IF proteins have long resisted crystallization and thus determination of their atomic structure. Since they represent the primary structural elements that determine the shape of the nucleus and the cell more generally, a major challenge is to arrive at a more rational understanding of how their nanomechanical properties effect the stability and plasticity of cells and tissues. Here, we review recent structural results of the coiled-coil dimer, assembly intermediates and growing filaments that have been obtained by a hybrid methods approach involving a rigorous combination of X-ray crystallography, small angle X-ray scattering, cryo-electron tomography, computational analysis and molecular modeling.