Hyperosmotic Stress Allosterically Reconfigures Betaine Binding Pocket in BetP

Sarala Tantirimudalige, Theresa Sophia Claire Buckley, Arun Chandramohan, Rebecca Michaela Richter, Christine Ziegler, Ganesh S. Anand

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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.

Original languageEnglish (US)
Article number167747
JournalJournal of Molecular Biology
Issue number17
StatePublished - Sep 15 2022

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Molecular Biology


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