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Structure and Mechanism of the Lactose Permease of Escherichia coli
Jeff Abramson,1Irina Smirnova,3Vladimir Kasho,3Gillian Verner,3H. Ronald Kaback,3*So Iwata1,2*
Membrane transport proteins that transduce free energy storedin electrochemical ion gradients into a concentration gradientare a major class of membrane proteins. We report the crystalstructure at 3.5 angstroms of the Escherichia coli lactose permease,an intensively studied member of the major facilitator superfamilyof transporters. The molecule is composed of N- and C-terminaldomains, each with six transmembrane helices, symmetricallypositioned within the permease. A large internal hydrophiliccavity open to the cytoplasmic side represents the inward-facingconformation of the transporter. The structure with a boundlactose homolog, ß-D-galactopyranosyl-1-thio-ß-D-galactopyranoside,reveals the sugar-binding site in the cavity, and residues thatplay major roles in substrate recognition and proton translocationare identified. We propose a possible mechanism for lactose/protonsymport (co-transport) consistent with both the structure anda large body of experimental data.
1 Department of Biological Sciences, Imperial College London, London SW7 2AZ, UK. 2 Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, UK. 3 Howard Hughes Medical Institute, Departments of Physiology and Microbiology, Immunology, and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
* To whom correspondence should be addressed. E-mail: ronaldk{at}hhmi.ucla.edu, s.iwata{at}imperial.ac.uk
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