Doing the Twist

The genes mapped in the Human Genome Project encode the chemical sequence of proteins. But uncovering a protein's genetic sequence without understanding the factors that determine its three-dimensional shape (the primary property influencing protein function) is much like having all the ingredients of a recipe but lacking its instructions.

Proteins are "born" unfolded. When first produced by the ribosomal factory they emerge as straight, unfurled strings, but must fold into their correct form to become functional. How does the "young" protein know which way to twist? Do "folding instructions" arrive with the genetic package, or do these tabula rasa proteins receive some help from nearby friends?

Turns out that living cells contain "molecular chaperones" which "counsel" young proteins and provide them with a secure environment in which to twist properly. These chaperones - themselves proteins - are the focus of research conducted by Prof. Amnon Horovitz, Head of the Weizmann Institute's Structural Biology Department. For instance, one "chaperone" molecule, called GroEL, is composed of two identical ring-like cones stacked back-to-back in such a way that a cavity, in which the twisting occurs, forms at each end.

How does the protein twist inside this chaperone? By attaching a fluorescent molecule onto two different sites of an unfolded protein molecule and using a laser beam to activate the system, one can follow the formation of the young protein via a microscope equipped with sophisticated light sensors. In a sense, molecular chaperones operate much like a biological machine, and Horovitz's research aims to uncover their behavior. Success with this ambitious project may someday enable us to build artificial molecular machines that would imitate the functions of "chaperones" and carry out a variety of mechanical processes at high efficiency and low cost.

Prof. Amnon Horovitz holds the Carl and Dorothy Bennett Chair of Biochemistry. His research is supported by the Asher and Jeanette Alhadeff Research Award.