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The mode of action of essential proteins involved in cancer and Alzheimer´s deciphered

Researchers determine the structure of nanomachine essential for functioning of mTOR

Researchers determine the structure of nanomachine essential for functioning of mTOR The principle that form follows function does not only apply to design and architecture. It also applies to biology. Every organism is a universe that lives thanks to the activities of tens of thousands of nanomachines, whose functions depend on their forms. Biologists say macromolecular complexes instead of nanomachines and structure instead of form, but the idea is the same: know the form and you will understand the function. Now, a group at the Spanish National Cancer Research Centre (CNIO) has helped determine the structure of a nanomachine essential for the functioning of another, mTOR, which plays fundamental roles in cancer and nutrition, aging, and other vital processes in the body.

CNIO and IRB Barcelona assemble the gamma-tubulin ring complex in vitro for the first time

Credit: CNIO Researchers from the Microtubule Organization lab, headed by Jens Lüders at IRB Barcelona, and the Macromolecular Complexes in DNA Damage Response Group, led by Oscar Llorca at the Spanish National Cancer Research Centre (CNIO), have achieved the first in vitro reconstitution of the human -tubulin ring complex (γTuRC), responsible for initiating microtubule formation. In addition, they revealed its 3D structure by cryo-electron microscopy. The key to their success lies in the identification of the RUVBL protein complex as an essential γTuRC assembly helper. Microtubules are a component of the cytoskeleton, which is essential for intracellular transport processes and cell division. Microtubules cannot form spontaneously in cells but require nucleation by the γTuRC. Mutations in γTuRC subunits cause neurodevelopmental defects such as microcephaly and have also been linked to defects in the retina.

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