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Moving Crystallographic Snapshots: A Mechanism for Transport Regulation in BetP

  • Christine Ziegler
  • Reinhard Krämer
Chapter
Part of the Springer Series in Biophysics book series (BIOPHYSICS, volume 17)

Abstract

The molecular understanding of secondary transport, in particular how transport activity is regulated, is one of the cutting-edge questions in biological science. A number of secondary transporters show regulation of transport activity, which plays an important role in stress-induced cellular responses. Transport activity is regulated in response to various external stimuli, which often are difficult to identify. Therefore, only a few regulated transporters are described to date; one of the best characterized amongst them is the Na+-coupled betaine symporter from Corynebacterium glutamicum, BetPCg. The biochemical background of stimulus sensing by activity regulation of BetPCg has been elucidated in detail both in cells and proteoliposomes. First insight into a molecular mechanism of regulated transport in BetP was obtained by the combination of two-dimensional (2D) and three-dimensional (3D) crystallization, functional measurements, spectroscopy, and bioinformatics. In the last 5 years several atomic structures of trimeric BetP were solved in different conformational states and under both activating and inactivating conditions. Thereby, the transport cycle of BetP was described in molecular detail; however, the dynamics of osmoregulation is still far from being understood. One major limiting factor on the way to a molecular mechanism is restrictions imposed by the crystalline environment, which may populate or exclude some of the functional important conformations. The example of BetP demonstrates how difficult it is to trap activation and regulation of a transporter in a crystal structure. In this chapter we will critically discuss the efforts in obtaining meaningful structural and functional data and how they are combined in a dynamic description of transport and regulation of a secondary carrier.

Keywords

Alternating access Secondary transport Membrane transport Conformational states Osmoregulation Activation Sodium coupling Oligomerization Stress response Signal transduction 

Notes

Acknowledgment

The authors would like to thank Lucy Forrest, Markus Becker, and Camilo Perez for inspiring discussions, which have contributed to topics discussed in this chapter. C.Z. want to thank Caroline Koshy and Belinda Faust for important inputs on transporter structure determination. The structural work on BetP (C.Z.) was supported by the DFG Collaborative Research Center 807: Transport and Communication across Biological Membranes, and the functional work (R.K.) by the DFG grant KR 693/10-2.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.University of Regensburg and MPI of BiophysicsFrankfurtGermany
  2. 2.University of CologneCologneGermany

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