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Journal of Bacteriology, March 2003, p. 1712-1718, Vol. 185, No. 5
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.5.1712-1718.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Structural Model for 12-Helix Transporters Belonging to the Major Facilitator Superfamily

Teruhisa Hirai,1 Jürgen A. W. Heymann,1 Peter C. Maloney,2 and Sriram Subramaniam1*

Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892,1 Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 212052

Received 8 October 2002/ Accepted 25 November 2002

The major facilitator superfamily includes a large collection of evolutionarily related proteins that have been implicated in the transport of a variety of solutes and metabolites across the membranes of organisms ranging from bacteria to humans. We have recently reported the three-dimensional structure, at 6.5 Å resolution, of the oxalate transporter, OxlT, a representative member of this superfamily. In the oxalate-bound state, 12 helices surround a central cavity to form a remarkably symmetrical structure that displays a well-defined pseudo twofold axis perpendicular to the plane of the membrane as well as two less pronounced, mutually perpendicular pseudo twofold axes in the plane of the membrane. Here, we combined this structural information with sequence information from other members of this protein family to arrive at models for the arrangement of helices in this superfamily of transport proteins. Our analysis narrows down the number of helix arrangements from about a billion starting possibilities to a single probable model for the relative spatial arrangement for the 12 helices, consistent both with our structural findings and with the majority of previous biochemical studies on members of this superfamily.


* Corresponding author. Mailing address: Laboratory of Biochemistry, National Institutes of Health, 50 South Drive, Room 4306, MSC 8008, Bethesda MD 20892-8008. Phone: (301) 594-2062. Fax: (301) 480-3834. E-mail: ss1{at}nih.gov.


Journal of Bacteriology, March 2003, p. 1712-1718, Vol. 185, No. 5
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.5.1712-1718.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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