The intracellular lipid-binding domain of human Na⁺/H⁺ exchanger 1 forms a lipid-protein co-structure essential for activity.

ABSTRACT: Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na⁺/H⁺-exchanger 1 (NHE1) regulates intracellular pH (pH_i) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE

SUBMITTER: Hendus-Altenburger R 

PROVIDER: S-EPMC7713384 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature