College of Liberal Arts & Sciences

Electron tomography and molecular modeling study of chemoreceptor organization

November 3, Tue 2009
1:00 pm, MRB 100 Conference Room

Dr. Xiongwu Wu

Laboratory of Computational Biology, National Heart Lung and Blood Institute, NIH

The movement of bacteria in response to external stimuli represents a paradigm of broad general interest for the understanding of mechanisms underlying signal transduction across cell membranes. Bacterial chemoreceptors respond to changes in concentration of extracellular ligands by undergoing conformational changes that initiate a series of signaling events, leading ultimately to regulation of flagellar motor rotation. Atomic structures for several domains of chemoreceptors, including the periplasmic ligand-binding domain, the cytoplasmic signaling domain and the HAMP domain are available, but the molecular architectures of an intact receptor dimer, or the functionally relevant trimer-of-dimer configuration have remained elusive. Here, we have used cryo-electron tomography combined with 3D averaging to determine the in situ 3D structure of receptor assemblies in bacterial cells that have been engineered to overproduce only the receptor for serine chemotaxis, Tsr, and lacking all other chemotaxis receptors and signaling components. We identified two major conformations of the chemotaxis receptors. Through comparative modeling and map-constrained molecular dynamics simulations, we obtained the assembly structures of tsr organized in a two dimensional array. We show that receptors are organized in trimer-of-dimer conformations with peripasmic domain, HAMP domain, and signal traction domain transiting between conformations. It is suggested that the position of the ligand binding domain and the HAMP domain play a pivotal role in mediating signal transduction across the cell membrane.

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