Helmholtz Gemeinschaft


(In situ) conformational changes of the Escherichia coli serine chemoreceptor in different signaling states

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supporting Material)

Item Type:Article
Title:(In situ) conformational changes of the Escherichia coli serine chemoreceptor in different signaling states
Creators Name:Yang, W. and Cassidy, C.K. and Ames, P. and Diebolder, C.A. and Schulten, K. and Luthey-Schulten, Z. and Parkinson, J.S. and Briegel, A.
Abstract:Tsr, the serine chemoreceptor in (Escherichia coli), transduces signals from a periplasmic ligand-binding site to its cytoplasmic tip, where it controls the activity of the CheA kinase. To function, Tsr forms trimers of homodimers (TODs), which associate (in vivo) with the CheA kinase and CheW coupling protein. Together, these proteins assemble into extended hexagonal arrays. Here, we use cryo-electron tomography and molecular dynamics simulation to study Tsr in the context of a near-native array, characterizing its signaling-related conformational changes at both the individual dimer and the trimer level. In particular, we show that individual Tsr dimers within a trimer exhibit asymmetric flexibilities that are a function of the signaling state, highlighting the effect of their different protein interactions at the receptor tips. We further reveal that the dimer compactness of the Tsr trimer changes between signaling states, transitioning at the glycine hinge from a compact conformation in the kinase-OFF state to an expanded conformation in the kinase-ON state. Hence, our results support a crucial role for the glycine hinge: to allow the receptor flexibility necessary to achieve different signaling states while also maintaining structural constraints imposed by the membrane and extended array architecture. IMPORTANCE: In (Escherichia coli), membrane-bound chemoreceptors, the histidine kinase CheA, and coupling protein CheW form highly ordered chemosensory arrays. In core signaling complexes, chemoreceptor trimers of dimers undergo conformational changes, induced by ligand binding and sensory adaptation, which regulate kinase activation. Here, we characterize by cryo-electron tomography the kinase-ON and kinase-OFF conformations of the (E. coli) serine receptor in its native array context. We found distinctive structural differences between the members of a receptor trimer, which contact different partners in the signaling unit, and structural differences between the ON and OFF signaling complexes. Our results provide new insights into the signaling mechanism of chemoreceptor arrays and suggest an important functional role for a previously postulated flexible region and glycine hinge in the receptor molecule.
Keywords:Tsr Chemoreceptor, Chemoreceptor Arrays, Chemotaxis, Cryo-EM, Electron Cryotomography
Publisher:American Society for Microbiology
Page Range:e00973
Date:2 July 2019
Official Publication:https://doi.org/10.1128/mBio.00973-19
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library