Author response: A tethered delivery mechanism explains the catalytic action of a microtubule polymerase
Year: 2014
Type: peer-review
Abstract: Dynamic filaments of proteins, called microtubules, have several important roles inside cells. Microtubules provide structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficking of proteins and molecules across the cell. The building blocks of microtubules are proteins called αβ-tubulin, which are continually added to and removed from the ends of a microtubule, causing it to grow and shrink. Other proteins that interact with the microtubules can help to speed up these construction and deconstruction processes. Ayaz et al. took a closer look at the structure of one particular family of proteins that make it easier for the microtubules to grow, using a technique called X-ray crystallography. The resulting images show two sites—called TOG1 and TOG2—on the enzymes that attach to the αβ-tubulin proteins. Ayaz et al. found that this binding can only occur when αβ-tubulin has a curved shape, which only happens when the tubulins are not included in, or are only bound weakly to the end of, a microtubule. Previous research suggested that the two binding sites might work together to provide ‘scaffolding’ that stabilizes the microtubule. However, genetic experiments by Ayaz et al. show that microtubules will grow even if one of the binding sites is missing. Both TOG1 and TOG2 bind to αβ-tubulin in the same way, and by using computer simulations Ayaz et al. found that this helps to speed up the growth of microtubules. This is because the enzyme's two sites concentrate the individual tubulin building blocks at the ends of the filament. For example, TOG2 could bind to the end of the microtubule, while TOG1 holds an αβ-tubulin protein nearby and ready to bind to the filament's end. This tethering allows the microtubules to be assembled more efficiently.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2984467720
