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Crystal structure of the ATP-binding subunit of an ABC transporter

Nature volume 396, pages 703–707 (1998)Cite this article

Abstract

ABC transporters (also known as traffic ATPases) form a large family of proteins responsible for the translocation of a variety ofcompounds across membranes of both prokaryotes and eukaryotes1. The recently completed Escherichia coli genome sequence revealed that the largest family of paralogous E. coli proteins is composed of ABC transporters2. Many eukaryotic proteins of medical significance belong to this family, such as the cystic fibrosis transmembrane conductance regulator (CFTR), the P-glycoprotein (or multidrug-resistance protein) and the heterodimeric transporter associated with antigen processing (Tap1–Tap2). Here we report the crystal structure at 1.5 Å resolution of HisP, the ATP-binding subunit of the histidine permease, which is an ABC transporter from Salmonella typhimurium. We correlate the details of this structure with the biochemical, genetic and biophysical properties of the wild-type and several mutant HisP proteins. The structure provides a basis for understanding properties of ABC transporters and of defective CFTR proteins.

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Figure 1: Crystal structure of HisP.
Figure 2: Diagram of the secondary structure of HisP.
Figure 3: Atomic details of the interactions of HisP (residues are boxed) with ATP (centre).
Figure 4: Locations of signal-independent HisP mutations in the crystal structure.
Figure 5: Sequence alignment of HisP and the NBDs of human CFTR.

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Acknowledgements

We thank J. Jancarik for crystallization of native HisP crystals, and D. S. King for carrying out mass-spectroscopy analysis on the native and Se-Met HisP proteins. The MAD data for this study were collected at the Lawrence Berkeley National Laboratory in the Macromolecular Crystallography Facility at beamline 5.0.2 in the Advanced Light Source. This facility is principally funded by the Office of Biological and Environmental Research of the US Department of Energy Offices with contributions from Lawrence Berkeley National Laboratory, Amgen, Roche Biosciences, the University of California, Berkeley, and Lawrence Livermore National Laboratory. This work has been supported by grants from the Health Effects and Life Sciences Research Division, Office of Biosciences and Environmental Research, Office of Energy Research of Department of Energy (to S.-H.K.) and from the NIH (to G.F.-L.A.).

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Authors and Affiliations

  1. E. O. Lawrence Berkeley National Laboratory, University of California at Berkeley, Berkeley, 94720, California, USA

    Li-Wei Hung & Sung-Hou Kim

  2. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, 94720, California, USA

    Iris Xiaoyan Wang, Kishiko Nikaido, Pei-Qi Liu & Giovanna Ferro-Luzzi Ames

  3. Department of Chemistry, University of California at Berkeley, Berkeley, 94720, California, USA

    Sung-Hou Kim

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Correspondence to Sung-Hou Kim.

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Hung, LW., Wang, I., Nikaido, K. et al. Crystal structure of the ATP-binding subunit of an ABC transporter. Nature 396, 703–707 (1998). https://doi.org/10.1038/25393

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