Structural studies of internmediate fillaments
Intermediate filaments (IFs) are one of the three principal components of the cytoskeleton of metazoan cells. The human body contains over 70 types of IF proteins, which can be classified in five major groups based on amino acid sequence and location within the cell including the nucleus. A large number of pathologies have been associated with mutations in IFs due to loss of structural functions or altered interactions with other proteins and or DNA. Unlike for microtubules and actin microfilaments, two other cytoskeletal filament systems, the structure of IFs is not completely resolved. The flexible nature of IF proteins, the presence of unstructured regions as well as complexity of the assembly are the main hindrances. The focus of this PhD research project is to further elucidate the atomic structure of the tetramer, an important IF assembly intermediate, as well as the 3D architecture of mature filaments. Vimentin and lamin A will be studied as the structurally distinct representatives of cytoplasmic and nuclear IF proteins, respectively. To this end x-ray crystallography and other biophysical techniques will be used.