Stanford researchers make first direct observation of 3-D molecule folding in real time

Stanford researchers make first direct observation of 3-D molecule folding in real time

All the crucial proteins in our bodies must fold into complex shapes to do their jobs. These snarled molecules grip other molecules to move them around, to speed up important chemical reactions or to grab onto our genes, turning them “on” and “off” to affect which proteins our cells make.

Recently, scientists have discovered that RNA-the stringy molecule that translates our genetic code into protein-can act a lot like a protein itself. RNA can form loopy bundles that shut genes down or start them up without the help of proteins. Since the discovery of these RNA clumps, called “riboswitches,” in 2002, scientists have been striving to understand how they work and how they form. Now, researchers at Stanford University are looking closer than ever at how the three-dimensional twists and turns in a riboswitch come together by grabbing it and tugging it straight. By physically pulling on this loopy RNA, they have determined for the first time how a three-dimensional molecular structure folds, step by step.

The researchers used a machine called an “optical trap” to grab and hold the ends of an RNA molecule with laser beams. Based on technology developed by Bell Labs researchers in 1986, the machine was designed by a team led by Steven Block, the Stanford W. Ascherman, M.D., Professor and a professor of applied physics and of biology. The optical trap allows them to hold the ends of the RNA tightly, so they can pull it pin-straight, then let it curl up again. In the Feb. 1 issue of Science, their paper, of which Block is senior author, describes the development of every loop and fold in one particular RNA riboswitch, and the energy it takes to form or straighten each one-an unprecedented achievement that opens the door for equally thorough studies of other molecules and their behaviors.

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