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bioRxiv · 10.1101/821090

Structure-function analyses of a keratin heterotypic complex identify specific keratin regions involved in intermediate filament assembly

Lee, C.-H.·Kim, M.-S.·Li, S.·Leahy, D. J.·Coulombe, P. A.
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Abstract

Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding IF structure is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6 [A] resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handle coiled coil, with participating -helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents the first atomic-resolution visualization of 2B-2B interactions consistent with the A22 dimer alignment and provide insight into the defects introduced by mutations in IF genes associated with human skin diseases.

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Lee, C.-H., Kim, M.-S., Li, S., Leahy, D. J., Coulombe, P. A.. 2019-10-29. Structure-function analyses of a keratin heterotypic complex identify specific keratin regions involved in intermediate filament assembly. https://doi.org/10.1101/821090

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