Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online May 29, 2008
Science DOI: 10.1126/science.1156213

Reports

Submitted on February 7, 2008
Accepted on May 19, 2008

Structural Basis of Trans-Inhibition in a Molybdate/tungstate ABC Transporter

Sabina Gerber 1{dagger}, Mireia Comellas-Bigler 1{dagger}, Birke A. Goetz 1, Kaspar P. Locher 1*

1 Institute of Molecular Biology and Biophysics, ETH Zurich HPK D14.3, 8093 Zurich, Switzerland.

* To whom correspondence should be addressed.
Kaspar P. Locher , E-mail: kaspar.locher{at}mol.biol.ethz.ch

{dagger}These authors contributed equally to this work.

Transport across cellular membranes is an essential process that is catalyzed by diverse membrane transport proteins. The turnover rates of certain transporters are inhibited by their substrates in a process termed trans-inhibition, whose structural basis is poorly understood. Here we present the crystal structure of a molybdate/tungstate ABC transporter (ModBC) from Methanosarcina acetivorans in a trans-inhibited state. The regulatory domains of the nucleotide-binding subunits are in close contact and provide two oxyanion binding pockets at the shared interface. By specifically binding to these pockets, molybdate or tungstate prevent ATPase activity and lock the transporter in an inward-facing conformation, with the catalytic motifs of the nucleotide-binding domains separated. This allosteric effect prevents the transporter from switching between the inward-facing and the outward-facing states, thus interfering with the alternating access and release mechanism.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Lipid bilayer regulation of membrane protein function: gramicidin channels as molecular force probes.
J. A. Lundbaek, S. A. Collingwood, H. I. Ingolfsson, R. Kapoor, and O. S. Andersen (2009)
J R Soc Interface
   Abstract »    Full Text »    PDF »
Specific Interactions between Four Molybdenum-Binding Proteins Contribute to Mo-Dependent Gene Regulation in Rhodobacter capsulatus.
J. Wiethaus, A. Muller, M. Neumann, S. Neumann, S. Leimkuhler, F. Narberhaus, and B. Masepohl (2009)
J. Bacteriol. 191, 5205-5215
   Abstract »    Full Text »    PDF »
The mechanism of ABC transporters: general lessons from structural and functional studies of an antigenic peptide transporter.
E. Procko, M. L. O'Mara, W. F. D. Bennett, D. P. Tieleman, and R. Gaudet (2009)
FASEB J 23, 1287-1302
   Abstract »    Full Text »    PDF »
The High-Affinity E. coli Methionine ABC Transporter: Structure and Allosteric Regulation.
N. S. Kadaba, J. T. Kaiser, E. Johnson, A. Lee, and D. C. Rees (2008)
Science 321, 250-253
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)