Bio-X grant recipient explores link between molecular chaperones and serious diseases

``You`ve got to know when to fold `em,`` says the famous country western song.

Sound advice for playing poker - or making proteins.

It turns out that nearly every molecule of protein produced in your body has to be folded into a specific, three-dimensional shape in order to function properly. Because it translates the linear genetic code into three dimensions, protein folding has been called the second, and more intractable, half of the genetic code.

X-rays of the protein hemoglobin, for example, reveal a complex molecule that resembles a ball of twisted ribbon - a unique shape that allows hemoglobin to carry oxygen through the bloodstream. If the molecule is folded incorrectly, oxygen will not be delivered.

The human body produces thousands of proteins, each with a distinct function and shape. Some resemble convoluted pretzels, while others are woven into intricate braids.

Biologists used to believe that every protein molecule folded spontaneously as it was being assembled inside the living cell, but recent studies show that many proteins actually need help getting into shape.

Enter molecular chaperones.

Discovered just over a decade ago, chaperones are small proteins that help bigger ones fold and assemble. Some chaperones literally serve as escorts, guiding and twisting newborn proteins into their correct shape.

``No one expected that a cell would require special machinery for protein folding,`` says molecular biologist Judith Frydman, ``but what we are finding is that almost every interesting protein needs a chaperone.``

Frydman, an assistant professor of biological sciences, is one of a handful of international researchers whose work has led to new discoveries about molecular chaperones and their vital role in sustaining life.

``Chaperones prevent proteins from folding prematurely or sticking to debris inside the cell,`` she says. ``Without chaperones, some cells get very, very sick.``


Contact: Mark Shwartz
Stanford University

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