NEWS OF THE W EEK
CHOLERA TURN-ON BIOCHEMISTRY: Chemical switch activates disease-enhancing toxin
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N IMPORTANT TOXIN behind cholera’s lethal-
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ity activates itself by clamping down on a signaling molecule found only in hosts susceptible to the disease, a new study shows. This newly discovered triggering process may be common to multiple bacteria that cause food- and waterborne illnesses. The bacterium that causes cholera, a diarrheal illness that can be deadly, contains RTX, which stands for repeats in toxin, a protein that is thought to enhance the severity of the SWITCH A flap disease. RTX is (blue) on a choleranontoxic until its enhancing toxin’s protease funcprotease enzyme tion is activated clamps down on inositol upon entering hexakisphosphate (stick), the host. Inveswhich orients the protein’s tigators have active site (yellow) for known that inoscatalysis (C is gray, P is itol hexakisphosorange, and O is pink). phate (IP6), a signaling molecule
SCIENTIFIC TEAMWORK COLLABORATION: Highest impact research comes from scientists at different universities, study says Scientists’ collaborators are becoming more likely to be a longdistance phone call away than a walk down the hallway. S HUTTERSTOCK
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CIENTISTS IN SEARCH of a collaborator might want to take a closer look at faculty from other universities rather than search the ranks of their own department. According to a new study, research teams made up of scientists from different universities are on the rise across all areas of science and engineering (Science, DOI: 10.1126/science.1158357). Furthermore, these multiuniversity teams produce the highest impact papers, provided their authors include researchers from top-tier schools. Brian Uzzi, Benjamin F. Jones, and Stefan Wuchty of Northwestern University’s Kellogg School of Management examined more than 3.4 million science and engineering papers published between 1975 and 2005. In the 1970s, very few publications came from collaborators at different universities, but by 2005, such collaborations accounted for about one-third of published papers. At the same time, single-author publications have steadily WWW.C E N- ONLI NE .ORG
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not found in bacteria but abundant in disease hosts, triggers RTX activation, but the activation mechanism has remained unclear. Now, a Stanford University team led by biochemist Matthew Bogyo and structural biologist K. Christopher Garcia suggests that IP6 regulates RTX by triggering a structural rearrangement in its protease (Science 2008, 322, 265). The team’s X-ray crystal structure of the protease reveals that a protein flap rich in basic amino acid residues clamps down on IP6’s phosphate groups. Biochemical experiments suggest that the action of that switch orients the active site on RTX and turns on its proteolysis function, activating the toxin. Although many proteases are turned on by binding to activator molecules at sites other than the active site, “generally, these activators are other proteins,” not signaling molecules like IP6, comments protease expert Guy S. Salvesen of the Burnham Institute for Medical Research, in La Jolla, Calif. The finding could corroborate suggestions that other protease families are activated similarly by small molecules, he adds. Bogyo agrees that this type of activation could be common, pointing out that several bacteria that cause gastrointestinal illnesses contain protease sequences similar to RTX’s. The team was unable to crystallize RTX in the absence of IP6. They hope to obtain an NMR structure of the toxin to look for movement and nail down how activation happens.—CARMEN DRAHL
declined, and collaborations between researchers at the same university have decreased slightly. The Northwestern team also found that on the basis of the number of citations, multiuniversity teams produced the highest impact papers. “Teams between schools did better than teams within schools, and teams within schools did better than solo authors,” Uzzi says. “So, a Harvard professor is better off working with a Princeton or a Stanford professor than he is working with another Harvard professor.” Uzzi tells C&EN that several factors probably drive the trend toward multi-institutional collaborations, including the increasingly specialized nature of science, a rise in the number of faculty who relocate, and greater acceptance of joint authorship in science. Surprisingly, Uzzi says, the advent of the Internet hasn’t had much impact in the growth of multiuniversity teamwork. “The trend toward collaboration before and after the Internet is basically the same, which means that the Internet couldn’t have affected what’s going on,” he notes. “This type of bird’s-eye view of scholarly publication trends provides valuable insights into the research enterprise and how it is becoming more collaborative and less localized,” comments Arthur B. Ellis, vice chancellor for research at the University of California, San Diego. “The social networks that drive these developments represent an important form of investment and need to be better understood.”—BETHANY HALFORD
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