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Scientists Determine Atomic Structure Of Lego-Like Molecule That Self-Assembles Into Cell's Cargo Capsule

Scientists have determined the atomic structure of the three-spoked molecule called clathrin which "self-assembles," Lego-like, into a protective sphere just inside cell membranes and safely transports nutrients, hormones and other cargo into our cells.

The versatile molecule, which spontaneously disassembles and recycles after each delivery, was recently shown by other researchers to be targeted by the HIV virus. Invading viruses dupe clathrin into sequestering the cell's CD4 immune molecules, thereby preventing them from launching a defense against the virus. Knowledge of clathrin's atomic-level structure may enable researchers to counter the virus's pernicious strategy.

"If you know the structure, you can start understanding how clathrin is regulated," says Frances M. Brodsky, Ph.D., a leading clathrin researcher and a professor of biopharmaceutical sciences, pharmaceutical chemistry and microbiology and immunology at the University of California San Francisco (UCSF) where the study was carried out.

Brodsky and colleagues report the research in the May 27 issue of the journal Nature.

The atomic structure hints at what one of the UCSF scientists terms a "universal coupling motif" -- a configuration possibly shared by all proteins capable of coming together, like clathrin, and enclosing vital materiel in membranes for safe transit. Such controlled transport is essential for supplying nutrients and vitamins to cells, for secretion of hormones and for signaling cells to change their fate.

"Likely many proteins that contribute to traffic flow will have this motif," says Robert Fletterick, co-author on the Nature paper and a 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."

At the scale of the entire molecule, clathrin is shaped som
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Contact: Wallace Ravven
wravven@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
26-May-1999


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