We studied the process of sodium/proton antiport in the NapA transporter. Through a combination of X-ray crystallography, biochemistry and computer simulations we could show that the antiporter undergoes a large conformational transition that resembles a *elevator*-like movement whereby a single domain moves up- and down through the membrane and carries a sodium ion with it.
Transition pathways in high dimensional spaces, such as the ones produced by advanced algorithms to sample large conformational changes in macromolecules, are difficult to analyze quantitatively. We introduce a method named Path Similarity Analysis (PSA) that enables us to quantify the similarity between two arbitrary paths and extract the atomic-scale determinants responsible for their differences. PSA is implemented in the MDAnalysis library.
A new crystal structure of the Escherichia coli NhaA dimer reveals a previously unidentified salt bridge between two highly conserved residues at the putative binding site. The combination of structural data with molecular dynamics simulations yields new insights into the transport mechanism.
Dr. E. J. Norminton on
Oliver Beckstein onOliver Beckstein onOliver Beckstein on
