NEWS OF THE WEEK PUMPING ACTION The bent and otherwise distorted helices seen in the structures of LacY (left) and GlpT (right) may play an important role in the conformational changes these proteins undergo. (Bound lactose homolog is shown in black.)
SCIENCE © 2003
SPECTRA
STRUCTURAL
BIOLOGY
MOLECULAR PUMPS X-ray structures will allow modeling of whole family of transporter proteins
S
CIENTISTS HAVE CAP-
tured high-resolution pictures of two previously elusive members of a family of membrane proteins that pump molecules across cell membranes against their concentration gradients [Science, 301, 610 and 616 (2003)}. The X-ray crystal structures of these two transporters Vill serve as models for this very interesting and medically import a n t family of proteins," comments National Cancer Institute biophysicist Sriram Subramaniam. Members of the "major facilitator superfamily" manage to move all kinds of cargo "uphill"—including sugars, antibiotics, and peptides— and have been implicated in antibiotic resistance, diabetes, and many other diseases. The membrane proteins power this thermodynamically unfavorable task with the energy harnessed by moving a second molecule down its
ADAPTED FROM SCIENCE © 2003
concentration gradient—that is, from a region of high concentration to low concentration. For the bacterial lactose permease LacY, a proton gradient powers the pumping of lactose. The bacterial transporter GlpTrelies on agradient of inorganic phosphate to drive the transport of glycerol-3phosphate. T h e flexibility shared by members of this protein family has made it difficult to study their structures. After years of trying, the 3.5-A LacY structure was solved by a team led by Howard
COLLECTION
Dow Donates Data To NIST
T
he National Institute of Standards & Technology has received a gift of more than 50,000 infrared spectra from Dow Chemical. The data will be evaluated for use in NIST's Chemistry WebBook, a free online resource for scientists. The IR spectra were collected over 40 years at Dow to characterize and identify numerous pure chemicals, including many first synthesized by Dow experimentally during product development or for analysis of process measurements. The contribution—250,000 documents—has been independently valued at $5 million. "This donation is focused on improving the scientific capabili-
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Hughes Medical Institute investigator and biochemist H. Ronald Kaback of the University of California, Los Angeles, and crystallographer So Iwata of Imperial College, London. Crystallographer Da-Neng Wang and his coworkers at New Y)rk University School of Medicine obtained the 33-A structure of GlpT. In both structures, a pair of six-helix domains are arranged like the two halves of a clam shell, partially enclosing a solvent-filled crevice that opens into the cytoplasm. The shell's "hinge" blocks access to the other side of the membrane. In the LacY structure, a lactose homolog is bound in the hydrophilic crevice. On the basis of the structure and the vast amount of biochemical data Kaback's lab has collected on LacY, Kaback and Iwata suggest that proton binding causes LacY^ two protein domains to pinch closed, forcing the hinged side open. This would provide a path for lactose to pass to the other side of the membrane. Wang's team proposes a similar mechanism for GlpT The molecular details of how a concentration gradient might be harnessed to power such a conformational change remain unclear, Subramaniam notes. To this end, both teams are working to trap their proteins in the opposite conformation.—AMANDA YARNELL
ty of the world," said Richard M. Gross, Dow corporate vice president for R&D, in making the formal presentation, which was attended by ACS President Elsa Reichmanis, NIST Director Arden L Bement, Jr. and several dozen government and industry officials. The donation was received by Commerce Department Deputy Secretary Samuel W. Bodman, who emphasized the importance of partnerships between the federal government and industry. The collection will significantly increase the data in NIST's WebBook (http://webbook.nist.gov/chemistry/). This database currently contains IR spectra for about 6,000 molecules in the vapor phase and about 10,000 in condensed phase. NIST officials hope that the Dow donation will encourage other companies to donate data.-DAVID HANSON
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