| Institution: | 1. Department of Dermatology, Yale University, New Haven, CT, 06520, USA;2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520, USA;1. Department of Agricultural Biotechnology, Centre for Food Safety and Toxicology, Centre for Food and Bioconvergence, Research Institute for Agriculture and Life Sciences, CALS, Seoul National University, Seoul, 08826, Republic of Korea;2. Department of Molecular Biology, College of Natural Science, Pusan National University, Busan, 46241, Republic of Korea;1. Department of Cell and Developmental Biology, University of Michigan, USA;2. Department of Cell and Developmental Biology, Vanderbilt University, USA;3. Department of Biomolecular and Chemical Engineering, Department of Biochemistry, Vanderbilt University, USA;1. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;2. Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;3. Department of Immunology, School of Basic Medical Sciences, Weifang Medical University, Weifang, China;4. School of Life Science, Westlake University, Hangzhou, Zhejiang, China;5. Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China;1. Institute for X-ray Physics, Georg August University Göttingen, Göttingen, Germany;2. School of Engineering and Applied Sciences and Department of Physics, Harvard University, Cambridge, USA;3. Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, USA;4. Biozentrum, University of Basel, Basel, Switzerland;5. B065 Functional Architecture of the Cell, German Cancer Research Center (DKFZ), Heidelberg, Germany |
| Abstract: | Intermediate filaments (IFs) are key players in multiple cellular processes throughout human tissues. Their biochemical and structural properties are important for understanding filament assembly mechanisms, for interactions between IFs and binding partners, and for developing pharmacological agents that target IFs. IF proteins share a conserved coiled-coil central-rod domain flanked by variable N-terminal ‘head’ and C-terminal ‘tail’ domains. There have been several recent advances in our understanding of IF structure from the study of keratins, glial fibrillary acidic protein, and lamin. These include discoveries of (i) a knob–pocket tetramer assembly mechanism in coil 1B; (ii) a lamin-specific coil 1B insert providing a one-half superhelix turn; (iii) helical, yet flexible, linkers within the rod domain; and (iv) the identification of coil 2B residues required for mature filament assembly. Furthermore, the head and tail domains of some IFs contain low-complexity aromatic-rich kinked segments, and structures of IFs with binding partners show electrostatic surfaces are a major contributor to complex formation. These new data advance the connection between IF structure, pathologic mutations, and clinical diseases in humans. |
