Mg2+-dependent mechanism of environmental versatility in a multidrug efflux pump

• DOI: 10.1016/j.str.2024.12.012
• Publication Date: 2025-01-13T15:41:52Z
• Authors: Benjamin Russell ...; Muhammad R. Uddin; Katie M. Kuo; Laila M.N. Shah; Nicola J. Harris; Paula J. Booth; Dietmar Hammerschmid; James C. Gumbart; Helen I. Zgurskaya; Eamonn Reading
• Keywords: Efflux

Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm are major drivers of among gram-negative bacteria. Cations, such as Mg2+, become concentrated within and, in contrast to cytoplasm, its pH is sensitive conditions outside cell. Here, we reveal an interplay between Mg2+ modulating structural dynamics periplasmic adapter protein, AcrA, function prototypical AcrAB-TolC pump from Escherichia coli. In absence AcrA becomes increasingly plastic acidic conditions, but when bound this ameliorated, resulting instead domain specific organization. We establish a unique histidine residue directs these essential for sustaining activity across acidic, neutral, basic regimes. Overall, propose conserves mobility ensure optimal rapidly changing environments commonly faced during bacterial infection colonization.