The E. coli BtuCD Structure: A Framework for ABC Transporter Architecture and Mechanism

American Association for the Advancement of Science (AAAS) - Tập 296 Số 5570 - Trang 1091-1098 - 2002
Kaspar P. Locher1, Allen T. Lee1, Douglas C. Rees1
1Howard Hughes Medical Institute and Division of Chemistry and Chemical Engineering, Mail Code 147-75CH, California Institute of Technology, Pasadena, CA 91125, USA.

Tóm tắt

The ABC transporters are ubiquitous membrane proteins that couple adenosine triphosphate (ATP) hydrolysis to the translocation of diverse substrates across cell membranes. Clinically relevant examples are associated with cystic fibrosis and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we report the crystal structure at 3.2 angstrom resolution of the Escherichia coli BtuCD protein, an ABC transporter mediating vitamin B 12 uptake. The two ATP-binding cassettes (BtuD) are in close contact with each other, as are the two membrane-spanning subunits (BtuC); this arrangement is distinct from that observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20 transmembrane helices grouped around a translocation pathway that is closed to the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette and appears to represent a conserved motif among the ABC transporters.

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We thank the staff at the Stanford Synchrotron Radiation Laboratory (SSRL) the Advanced Photon Source (APS) the Advanced Light Source (ALS) and the National Synchrotron Light Source (NSLS) for their support during crystal screening and data collection. We also thank M. Barclay R. Bass O. Einsle I. Locher-Hinderling and P. Strop for helpful discussions. We further thank M. Day for assistance in obtaining the cyclotetravanadate coordinates and L. Ackerman and J. Bercaw for their help in the synthesis of inorganic clusters during the search for derivatives. The coordinates of the BtuCD transporter with bound cyclotetravanadate have been deposited in the Protein Data Bank (www.rcsb.org/pdb) with access code IL7V.

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American Association for the Advancement of Science (AAAS)

Tập 296 Số 5570

1091-1098

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