DYNEIN’S MOTOR REVEALED STRUCTURAL BIOLOGY: Researchers
solve first crystal structure of long-elusive molecular motor
EARLY 50 YEARS after the discovery of the walking molecular motor dynein, researchers have finally solved the first X-ray crystal structure of its massive motor domain. The milestone will permit researchers to tweak and tune the molecular engine that drives the transport of neurotransmitter vesicles, mRNA, and nuclei around biological cells and powers the beating of flagella and cilia. Seven years after he first took a stab at solving dynein’s crystal structure as a postdoc, Andrew P. Carter, now a structural biologist at the Medical Research Council, in Cambridge, England., and Carol Cho, a graduate student in Ronald D.
N The structure of dynein’s motor has been solved. Missing from the structure are the feet at the end of the stalk and the cargo domain.
UNCERTAINTY PLAGUES ANTHRAX PROBE INVESTIGATION: Molecular techniques
don’t identify the source of anthrax used in 2001 attacks, NRC report says
S
CIENCE ALONE does not pinpoint the source
of the anthrax used in a string of deadly bioterrorism attacks launched via the U.S. mail in 2001, concludes an expert committee of the National Research Council (NRC) in a report released on Feb. 15 in Washington, D.C. On the same day, Rep. Rush D. Holt (D-N.J.) reintroduced the Anthrax Attacks Investigation Act, which would establish a congressional investigation of the FBI’s work and consider a wider scope of evidence than did the NRC committee. NRC’s review was limited to the scientific work that traced the origins of the anthrax to a flask under the control of government biodefense researcher Bruce E. Ivins. The anthrax mailings themselves originated from a postal box in Holt’s central New Jersey district. Although it casts doubt, the carefully AFP/FB I
A technician at the Army’s Fort Detrick biomedical research laboratory in Frederick, Md., opening a letter suspected of containing anthrax in December 2001.
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Vale’s cell biology lab at the University of California, San Francisco, finally elucidated the protein motor at 6-Å resolution (Science, DOI: 10.1126/science.1202393). “This is a major breakthrough,” comments Stan Burgess, a biologist at Leeds University, in England, who publishes electron microscopy images of molecular motors. “Even though it is still not yet atomic resolution, the structure will transform the field of dynein research because it means we can now insert chemical crosslinks and do mutagenesis to really see how [the motor] works.” The exact details of how dynein works have been just “arm waving” up until now, Burgess adds. Dynein has been the most elusive to crystallize of the three molecular motors known to walk around cells on protein tracks. Structures of the other motors, myosin and kinesin, were more easily solved, likely because their motors are one-tenth of the size of dynein’s. To get the X-ray crystal structure of dynein’s motor, the team had to remove the feet at the end of dynein’s lollipop-like structure, which walk along the protein track. They also had to remove dynein’s cargo domain, whose shape selects for the right freight. Carter says he will now try to get a higher resolution picture of the motor domain to help figure out how the binding of adenosine triphosphate into four pockets in the motor powers the large conformational changes that permit dynein to step forward.—SARAH EVERTS
worded NRC report—and its stoic delivery at a press briefing on the same day—avoids making any judgment about the FBI’s conclusion that Ivins masterminded and carried out the attacks. Ivins killed himself once he became the chief suspect in the FBI probe. Amid heavy criticism, the bureau closed its case against Ivins a year ago, only months after the NRC committee began its work (C&EN Online Latest News, Feb. 23, 2010). “We will not offer any view on the guilt or innocence of any person,” committee Chair Alice P. Gast, a physical chemist who is also president of Lehigh University, said at the press briefing, echoing previous statements. She said the committee did not review any other forensic evidence developed by the FBI, focusing solely on the molecular techniques the FBI used to identify and characterize the spores and then trace their origin. On that basis, the committee could not rule out other sources of the anthrax used in the attacks. The report “makes clear there are still questions to be answered and still lessons to be learned about the FBI’s investigation into the attacks,” Holt said in a statement. “It would take a credulous person to believe the circumstantial evidence that the FBI used to draw its conclusions with such certainty.” In response to the report, the FBI notes that “the scientific findings in this case provided investigators with valuable investigative leads.” The bureau says it was the totality of evidence gathered, however, that led to its ultimate conclusion about Ivins.—WILLIAM SCHULZ
FEBRUARY 21, 2011
ANDREW CARTER
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