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See Inside April 2011

The Orderly Chaos of Proteins

To do their magic in the cell, proteins must fold into rigid shapes—or so standard wisdom says. But a more tangled story is beginning to emerge



Illustration by AXS Biomedical Animation Studio

Proteins are the stuff of life. They are the eyes, arms and legs of living cells. Even DNA, the most iconic of all molecules in biology, is important first and foremost because it contains the genes that specify the makeup of proteins. And the cells in our body differ from one another—serving as neurons, white blood cells, smell sensors, and so on—largely because they activate different sets of genes and thus produce different mixtures of proteins.

Given these molecules’ importance, one would think biologists would have long figured out the basic picture of what they look like and how they work. Yet for decades scientists embraced a picture that was incomplete. They understood, quite properly, that proteins consist of amino acids linked together like beads on a string. But they were convinced that for a protein to function correctly, its amino acid chain first had to fold into a precise, rigid configuration. Now, however, it is becoming clear that a host of proteins carry out their biological tasks without ever completely folding; others fold only as needed. In fact, perhaps as many as one third of all human proteins are “intrinsically disordered,” having at least some unfolded, or disordered, parts.

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