Chaperone Molecules Guide Assembly of Bacterial Pili

Investigators using x-ray crystallography have described the mechanism by which bacteria assemble pili, the minute hair-like fibers that allow them to cling to cells that line areas of the body such as the digestive, respiratory, or urinary tracts. Their findings were published in the November 15, 2002, issue of Cell.

Earlier work had shown that the molecules incorporated into the pili were associated with "chaperone molecules” which insured that the pili components bound at the correct site. In the current study, researchers from Washington University (St. Louis, MO, USA) found that pili were assembled from subunits within the bacterial membrane, and that assembly occurred via a donor strand exchange mechanism in which the N-terminal extension of one subunit replaced a chaperone strand that transiently occupied a groove in the neighboring subunit.

The chaperone primed the subunit for assembly by holding the groove in an open, activated conformation. During donor strand exchange, the subunit underwent a topological transition that triggered the closure of the groove and sealed the N-terminal extension in place. It was this topological transition, made possible only by the priming action of the chaperone, that drove subunit assembly into the pili fibers.

"Discovering that the fibers consist of interlocking tails explains why bacterial pili are so durable and able to resist harsh conditions in the laboratory,” explained senior author Dr. Scott J. Hultgren, professor of molecular microbiology at Washington University. "Our findings should lead to new drugs to treat urinary tract infections by blocking the formation of these protein fibers. They also should improve our general understanding of how disease-causing bacteria build, fold and secrete proteins that enable them to cause disease.”



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