Current opinion in structural biology

0959-440X 15 4 2005 Aug Current opinion in structural biology Curr. Opin. Struct. Biol. TonB-dependent outer membrane transport: going for Baroque? 394-400 The import of essential organometallic micronutrients (such as iron-siderophores and vitamin B(12)) across the outer membrane of Gram-negative bacteria proceeds via TonB-dependent outer membrane transporters (TBDTs). The TBDT couples to the TonB protein, which is part of a multiprotein complex in the plasma (inner) membrane. Five crystal structures of TBDTs illustrate clearly the architecture of the protein in energy-independent substrate-free and substrate-bound states. In each of the TBDT structures, an N-terminal hatch (or plug or cork) domain occludes the lumen of a 22-stranded beta barrel. The manner by which substrate passes through the transporter (the "hatch-barrel problem") is currently unknown. Solution NMR and X-ray crystallographic structures of various TonB domains indicate a striking structural plasticity of this protein. Thermodynamic, biochemical and bacteriological studies of TonB and TBDTs indicate further that existing structures do not yet capture critical energy-dependent and in vivo conformations of the transport cycle. The reconciliation of structural and non-structural experimental data, and the unambiguous experimental elucidation of a detailed molecular mechanism of transport are current challenges for this field. Department of Molecular Physiology and Biological Physics, University of Virginia, PO Box 800736, Charlottesville, VA 22908-0736, USA. mwiener@virginia.edu Wiener Michael C MC eng DK 59999 DK NIDDK Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Review