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Macromolecular transport complex in motion

November 2014. ABC transporters are a large family of macromolecular protein complexes located in cell membranes. These transporters, called "ABC" because of their ATP-binding cassette, are present both in prokaryotic organisms such as bacteria, and eukaryotic organisms, including humans. ABC transporters fulfill a variety of essential functions in organisms, the details of which are only partly understood despite their major medical significance in antibiotic and cancer drug resistance and other human diseases.

Recently an international team of scientists has been able for the first time to establish the detailed structure of an asymmetric ABC transport complex at a very high resolution.  The elucidation of the subnanometre-resolution structure of detergent-solubilized TmrAB has been possible through a collaboration of research groups in San Francisco (Robert Stroud, Charles Craik and Yifan Cheng at the University of California) and Frankfurt/Main (Robert Tampé, Institute of Biochemistry, Goethe University Frankfurt). The TmrAB structure reported was recorded by single-particle electron cryomicroscopy and is in a nucleotide-free, inward-facing conformation. The study spanned five years and only the combination of different methods including physical, biotechnological, biochemical and structural biology approaches made the major breakthrough possible. The results were published on 2 November 2014 by the prestigious journal Nature,

TmrAB is a heterodimeric ABC exporter from the thermophilic Gram-negative eubacterium Thermus thermophilus. It is homologous to various multidrug transporters and contains one degenerate site with a non-catalytic residue next to the Walker B motif.  The reconstructions of the team resolve characteristic features of ABC transporters, including helices in the transmembrane domain and nucleotide-binding domains. A cavity in the transmembrane domain is accessible laterally from the cytoplasmic side of the membrane as well as from the cytoplasm, indicating that the transporter lies in an inward-facing open conformation. The two nucleotide-binding domains remain in contact via their carboxy-terminal helices. Comparisons between the new structure and the crystal structures of other ABC transporters suggest a possible trajectory of conformational changes that involves a sliding and rotating motion between the two nucleotide-binding domains during the transition from the inward-facing to outward-facing conformations. More ...


Robert Tampé
Goethe-University Frankfurt
Campus Riedberg
Tel.: +49 (0)69 798-29475


Full publication:
Kim JM, Wu, S, Tomasiak T, Mergel C, Winter MN, Stiller S, Robles-Colmanares Y, Stroud RM*, Tampé R*, Craik CS*, Cheng Y* (2014) Subnanometer cryo-EM structure of a nucleotide free heterodimeric ABC exporter. Nature. Published online 2 Nov 2014, doi:10.1038/nature13872 (*corresponding authors). More ...