THE MYSTERY OF INTERMEDIATE FILAMENTS: STRUCTURAL PERSPECTIVE

O. Medalia | Deparment of Biochemistry, University of Zurich, Switzerland

Intermediate filaments (IFs) are a diverse component of the cytoskeleton that exhibit remarkable cellular and tissue specificity. Their distinctive mechanical characteristics, including extraordinary elasticity, tensile strength, and distinctive stiffening behaviours under strain and compression, are pivotal for the mechanical resilience of cells and the integrity of tissues. The distinguishing characteristics of these elements are attributable to their intricate, hierarchical architecture, which differs fundamentally from the architectures of other cytoskeleton elements, such as actin and microtubules. The IFs family of proteins consists of over 70 distinct proteins, which are divided into six subtypes based on their sequence. Nevertheless, does this classification offer any insight into their assembly, structure, and functions? IFs possess a broad repertoire of cellular functions, including the provision of structural support to cells, as well as active roles in mechanical support and signaling pathways. Consequently, it has been demonstrated that defects in IFs are associated with more than 100 diseases. Our understanding of IF assembly, disassembly and the structure of the resulting mature filaments remains in its infancy and is mostly restricted to in vitro experiments. Recently, we have determined the first two structure of assembled IFs, from cellular assembled filaments. This work indicates fundamental structural differences between IFs but also the general plan of assembly.