United Press International - Wednesday, May 26, 1999
Lidia Wasowicz, UPI Science Writer

The molecule, called clathrin, has the uncanny ability to assemble itself like so many Lego blocks inside the cell membrane so it can transport, unimpeded, nutrients, hormones and other essential cellular cargo.

Scientists say knowing the intimate details of the molecule's three- legged structure may eventually help them outwit the human immunodeficiency virus, HIV, which causes acquired immune deficiency syndrome, AIDS, before it can fully implement its deadly strategy.

Clever clathrin disassembles its three-spoked structure and recycles itself following each delivery.

"The cell has figured out how to regulate the input of nutrients, hormones and other vital molecules," said Frances Brodsky, professor of biopharmaceutical sciences, pharmaceutical chemistry and microbiology and immunology at the University of California, San Francisco.

"Central to that process is clathrin's capacity to first form a cage to transport its cargo, then disassemble, unload the cargo and finally recycle itself. It's a versatile molecule with a structure that determines its self-assembling and disassembling properties."

Its role in HIV progression came to light when scientists found how invading viruses trick the molecule into sequestering key disease fighting molecules behind a protective sphere inside cell membranes. Once isolated in such a fashion, these infection fighters, called CD4 immune molecules, are thwarted in their efforts to defend the body against invading microbes. Now that the structure of clathrin has come to light in atomic detail, researchers are hopeful they can eventually come up with measures to counter HIV's strategy.

"If you know the structure, you can start understanding how clathrin is regulated," said Brodsky, lead author of the study that will be reported Thursday in the British journal Nature.

What is of particular interest to the scientists is what one of them calls the "universal coupling motif." This style of configuration may, in fact, be common to all proteins that, like clathrin, can self- assemble into protective enclosures around vital material in need of safe passage.

"Such controlled transport is essential for supplying nutrients and vitamins to cells, for secretion of hormones and for signaling cells to change their fate," said study co-author Joel Ybe, assistant research biochemist at UCSF.

"Likely many proteins that contribute to traffic flow will have this motif," said study co-author Robert Fletterick, UCSF professor of biochemistry and biophysics. "Several have already been identified. The unmistakable footprint of the motif has just shown up in a protein involved in docking cells that are transported in membranous vessels in all animals and plants."
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