Site-specific chemistry on the microtubule polymer.
Microtubules are hollow tube-like biological polymers required for transport in diverse cellular contexts and are important drug targets. Microtubule function depends on interactions with associated proteins and post-translational modifications at specific sites located on its interior and exterior surfaces. However, we lack strategies to selectively perturb or probe these basic biochemical mechanisms. In this work, by combining amber suppression-mediated non-natural amino acid incorporation and tubulin overexpression in budding yeast, we demonstrate, for the first time, a general strategy for site-specific chemistry on microtubules. Probes and labels targeted to precise sites on the interior and exterior surfaces of microtubules will allow analysis and modulation of interactions with proteins and drugs, and elucidation of the functions of post-translational modifications.
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, New York 10065, USA.
Ralph E
RE
Kleiner
Shih-Chieh
SC
Ti
Tarun M
TM
Kapoor
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D014404:Tubulin / Q000096:biosynthesis / Q000737:chemistry
D000596:Amino Acids; D011108:Polymers; D014404:Tubulin