6EC0

Crystal structure of the wild-type heterocomplex between coil 1B domains of human intermediate filament proteins keratin 1 (KRT1) and keratin 10 (KRT10)

Summary for 6EC0

• Entry DOI: 10.2210/pdb6ec0/pdb
• Related: 6E2J
• Descriptor: Keratin 1, Keratin, type I cytoskeletal 10, CADMIUM ION, ... (6 entities in total)
• Functional Keywords: keratin, intermediate filament, coiled-coil, skin, protein fibril
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 25570.62

Authors

Eldirany, S.A.,Lomakin, I.B.,Bunick, C.G. (deposition date: 2018-08-07, release date: 2019-05-15, Last modification date: 2024-04-03)

Primary citation

Eldirany, S.A.,Ho, M.,Hinbest, A.J.,Lomakin, I.B.,Bunick, C.G.
Human keratin 1/10-1B tetramer structures reveal a knob-pocket mechanism in intermediate filament assembly.
Embo J., 38:-, 2019

PubMed Abstract: To characterize keratin intermediate filament assembly mechanisms at atomic resolution, we determined the crystal structure of wild-type human keratin-1/keratin-10 helix 1B heterotetramer at 3.0 Å resolution. It revealed biochemical determinants for the A mode of axial alignment in keratin filaments. Four regions on a hydrophobic face of the K1/K10-1B heterodimer dictated tetramer assembly: the N-terminal hydrophobic pocket (defined by L227, Y230, F231, and F234), the K10 hydrophobic stripe, K1 interaction residues, and the C-terminal anchoring knob (formed by F314 and L318). Mutation of both knob residues to alanine disrupted keratin 1B tetramer and full-length filament assembly. Individual knob residue mutant F314A, but not L318A, abolished 1B tetramer formation. The K1-1B knob/pocket mechanism is conserved across keratins and many non-keratin intermediate filaments. To demonstrate how pathogenic mutations cause skin disease by altering filament assembly, we additionally determined the 2.39 Å structure of K1/10-1B containing a S233L mutation linked to epidermolytic palmoplantar keratoderma. Light scattering and circular dichroism measurements demonstrated enhanced aggregation of K1/K10-1B in solution without affecting secondary structure. The K1/K10-1B octamer structure revealed S233L causes aberrant hydrophobic interactions between 1B tetramers.

PubMed: 31036554
DOI: 10.15252/embj.2018100741

Experimental method

X-RAY DIFFRACTION (2.983 Å)