5 research outputs found

    Single-molecule studies of flavivirus envelope dynamics: Experiment and computation

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    10.1016/j.pbiomolbio.2018.09.001PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY14338-5

    Hyperosmotic Stress Allosterically Reconfigures Betaine Binding Pocket in BetP

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    The transporter BetP in C. glutamicum is essential in maintaining bacterial cell viability during hyperosmotic stress and functions by co-transporting betaine and Na+ into bacterial cells. Hyperosmotic stress leads to increased intracellular K+ concentrations which in turn promotes betaine binding. While structural details of multiple end state conformations of BetP have provided high resolution snapshots, how K+ sensing by the C-terminal domain is allosterically relayed to the betaine binding site is not well understood. In this study, we describe conformational dynamics in solution of BetP using amide hydrogen/deuterium exchange mass spectrometry. These reveal how K+ alters conformation of the disordered C- and N-terminal domains to allosterically reconfigure transmembrane helices 3, 8, and 10 to enhance betaine interactions. A map of the betaine binding site, at near single amino acid resolution, reveals a critical extrahelical H-bond mediated by TM3 with betaine. (C) 2022 Elsevier Ltd. All rights reserved
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