A multi-substrate single-file model for ion-coupled transporters.

AUTOR(ES)

Su, A

RESUMO

Ion-coupled transporters are simulated by a model that differs from contemporary alternating-access schemes. Beginning with concepts derived from multi-ion pores, the model assumes that substrates (both inorganic ions and small organic molecules) hop a) between the solutions and binding sites and b) between binding sites within a single-file pore. No two substrates can simultaneously occupy the same site. Rate constants for hopping can be increased both a) when substrates in two sites attract each other into a vacant site between them and b) when substrates in adjacent sites repel each other. Hopping rate constants for charged substrates are also modified by the membrane field. For a three-site model, simulated annealing yields parameters to fit steady-state measurements of flux coupling, transport-associated currents, and charge movements for the GABA transporter GAT1. The model then accounts for some GAT1 kinetic data as well. The model also yields parameters that describe the available data for the rat 5-HT transporter and for the rabbit Na(+)-glucose transporter. The simulations show that coupled fluxes and other aspects of ion transport can be explained by a model that includes local substrate-substrate interactions but no explicit global conformational changes.

Documentos Relacionados

• Transport properties of single-file pores with two conformational states.
• Modeling the microbial growth of two Escherichia coli strains in a multi-substrate environment
• Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore.
• Proton transport across transient single-file water pores in a lipid membrane studied by molecular dynamics simulations.
• Disinfection and outcome of root canal treatment using single-file or multifile systems and Ca(OH)2 medication