Glial Fibrillary Acidic Protein - Structure

Structure

Type III intermediate filaments contain three domains, named the head, rod and tail domains. The specific DNA sequence for the rod domain may differ between different type III intermediate filaments, but the structure of the protein is highly conserved. This rod domain coils around that of another filament to form a dimer, with the N-terminal and C-terminal of each filament aligned. Type III filaments such as GFAP are capable of forming both homodimers and heterodimers; GFAP can polymerize with other type III proteins or with neurofilament protein (NF-L). Interestingly, GFAP and other type III IF proteins cannot assemble with keratins, the type I and II intermediate filaments: in cells that express both proteins, two separate intermediate filament networks form, which can allow for specialization and increased variability.

To form networks, the initial GFAP dimers combine to make staggered tetramers, which are the basic subunits of an intermediate filament. Since rod domains alone in vitro do not form filaments, the non-helical head and tail domains are necessary for filament formation. The head and tail regions have greater variability of sequence and structure. In spite of this increased variability, the head of GFAP contains two conserved arginines and an aromatic residue that have been shown to be required for proper assembly.