Conformational free-energy landscapes of a Na⁺/Ca²⁺ exchanger explain its alternating-access mechanism and functional specificity.

ABSTRACT: Secondary-active transporters catalyze the movement of myriad substances across all cellular membranes, typically against opposing concentration gradients, and without consuming any ATP. To do so, these proteins employ an intriguing structural mechanism evolved to be activated only upon recognition or release of the transported species. We examine this self-regulated mechanism using a homolog of the cardiac Na⁺/Ca²⁺ exchanger as a model system. Using advanced computer simulations, we map out the complete functional cycle of this transporter, including unknown conformations that we validate against existing experimental data. Calculated free-energy landscapes reveal why this transporter functions as an antiporter rather than a symporter, why it specifically exchanges N

SUBMITTER: Marinelli F 

PROVIDER: S-EPMC9928037 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature