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Freeze-frame microscopy captures molecule's 'lock-and-load' on DNA

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Cornelius Jones
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Pushing the limits of cryo-electron microscopy, University of California, Berkeley, scientists have captured freeze-frames of the changing shape of a huge molecule, one of the body's key molecular machines, as it locks onto DNA and loads the machinery for reading the genetic code.

Because of its many moving parts and large size, however, TFIID's 3D structure has been hard to capture: the moving parts become a blur.

Cryo-EM, an imaging technique whose discoverers garnered the 2017 Nobel Prize in Chemistry, is the only way to obtain a snapshot of bulky, floppy structures like this.

"These structures give you the potential for rationally designing small molecules that will disturb the normal function, because now we don't have just a single structure, we have many structures, which is even more powerful because we can target the motion that we are seeing right now," said Eva Nogales, a UC Berkeley professor of molecular and cell biology and a faculty scientist at Lawrence Berkeley National Laboratory.

Nogales and her colleagues, most prominently UC Berkeley graduate students Avinash Patel and Robert Louder, posted their findings online this week in advance of print publication in the journal Science.

Eva's structures are going to change that.

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