Figure 2. Molecular interactions contributing to intermediate filament assembly.

(A) Schematic of an intermediate filament (IF) depicting the four major alignments of anti-parallel tetramers believed to occur within a unit length filament (ULF) and mature IF. The model is based on anti-parallel tetramers being the building block of IFs because of their stability, which comes largely from A₁₁ knob-pocket interactions. Octamers form longitudinally via A_CN and A₂₂ interactions, the latter of which may be stabilized in part by contacts identified in the “ID1” interface. Octamers are joined in an anti-parallel orientation via A₁₂ interactions, providing lateral filament growth, and further association of octameric units leads to ULF formation. (B) The ID1 interaction involves many K14 residues (yellow) and a few K5 residues (blue) at the N and C termini of the K5/K14 2B domain (PDB ID 6JFV). The highly conserved 2B residues TYR*LLEG (orange) are present at the C-terminus of the structure. Electrostatic and hydrophobic surfaces of K5/K14–2B show that the TYR*LLEG motif (asterisk) occupies an acidic portion of the molecule. The electrostatic and hydrophobic surfaces were calculated using APBS/PDB2PQR and UCSF Chimera software. (C) The 1B anchoring knob-hydrophobic pocket mechanism that stabilizes A₁₁ tetramer formation is structurally homologous in four coil 1B structures: heteromeric K1/K10 and homomeric vimentin, lamin A/C, and GFAP.