Development of peptides binding to the inside of microtubules toward functionalization of microtubules

Microtubules, one of the cytoskeletons, are tubular structures (typically 15 nm in inner diameter) composed of tubulin proteins and play important roles in cellular function. Since microtubules exhibit motility by combining with motor proteins, they attracted attention as components of motile materials (active matter). Although there have been many reports on the introduction of functional molecules to the "external" surface of microtubules, little attention has been paid to the "inner" surface of microtubules. Recently, a number of proteins that bind to the inner surface of natural microtubules have been discovered, and their significance has been attracting attention. We have developed a Tau-derived peptide (TP) that binds to the inner surface of microtubules. By using TP, various nanostructures such as proteins, metal nanoparticles, and cyclic peptides were introduced inside microtubules. We found that the structures and properties of microtubules were modulated dependent on the encapsulated molecules. TP can also bind to intracellular microtubules, and we have succeeded in stabilizing microtubules and inducing cell death based on the light-induced covalent bond formation between TP and microtubules. Recently, we have found that TP-fused proteins can induce the generation of various microtubule superstructures such as doublet microtubules, branched structures, and aster (radial assembly) structures. Thus, we are developing new principles to modulate the structures and functions of microtubules from the inside by peptide-based molecular design. Future applications include the development of microtubule-based materials for nanodevices and molecular robots, and cell manipulation by controlling the structures and functions of intracellular microtubules.

Representative papers

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  • ACS Omega, 4, 11245-11250 (2019).
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  • ChemBioChem, 24, e202200782 (2023). ChemBioTalents 2022/23
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