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Blueprints of the Protein Factory
 
 
 

The Tunnel and the Donut

These images show Frank's 3D reconstruction of a yeast ribosome (beige) bound with the protein-conducting channel (blue), which attaches to the endoplasmic reticulum. The front view shows the donut shape of the PCC. The side view cross-section shows how the ribosome intersubunit tunnel aligns with the PCC donut hole. The stem of the ribosome (arrow) connects it to the PCC donut. The space between the two subunits (40S & 60S) is marked by an asterisk. The dashed-line indicates the export passageway for new proteins.

The uniformity of the earth's life, more astonishing than its diversity, is accountable by the high probability that we derived, originally, from a single cell. It is from the progeny of this parent cell that we take our looks; we still share genes aro und, and the resemblance of the enzymes of grasses to those of whales is a family resemblance.

--Lewis Thomas, The Lives of a Cell

 

All cells come from cells. It's a basic proposition of life. Each of us started as a single fertilized cell, a minuscule volume containing all the equipment needed to sustain itself, thrive and multiply, along with the instructions for creating the divers e, intricate multi-cellular organization of full-grown human life.

A cell is so small that not until 300 years ago, with the invention of light microscopes, did we learn there was such a thing. Now we know this tiny volume, 1,000 times smaller than the tip of a ballpoint pen, itself contains an energetic, teeming world o f small and large structures, moving parts, interacting subunits, a world easily more complicated and active than rush-hour Manhattan.

In the 1940s, a new tool, the electron microscope, gave scientists their first look at the details of structure within the cell. Since then biologists have pieced together a basic map of the intracellular world, one of the most essential components of whi ch is ribosomes, the miniature factories that build new proteins.

Three years ago, using the electron microscope in a powerful new way -- relying on computational methods to construct 3D images from 2D samples, Joachim Frank produced the first detailed, 3D picture of this protein factory. A senior scientist at the Wadsworth Center for Laboratories and Research in Albany, New York, Frank in 1996 followed his 1995 breakthrough with detailed views of the ribosome's inner space, images that show clearly for the first time how transfer- RNA molecules interact with the ribosome as they bring amino-acids to form the nascent protein.

Last year, Frank ported his software system to NCSA, gaining the advantage of more powerful computing, and at the same time making his imaging method more useful to others -- through the infrastructure of the National Computational Science Alliance. Since then, using the SGI/CRAY Origin2000, Frank and his colleagues placed another piece of the ribosome jigsaw puzzle. Their recent results (Science, Dec. 19, 1997) trace the pathway followed by a freshly minted protein chain as it slips out the ribosome back door, actually the exit from a tunnel, into a donut-shaped opening in the intracellular membrane known as the endoplasmic reticulum.

The key to these revealing -- and to biologists invaluable -- pictures of ribosome structure is "single-particle reconstruction," a method of electron-microscopy imaging that Frank's team at the Wadsworth Center developed and refined over 20 years of work .

   
 
 

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Access Online | Posted 3-31-1998