Su A, Mager S, Mayo S L, Lester H A
Division of Physics, Mathematics and Astronomy, California Institute of Technology, Pasadena 91125, USA.
Biophys J. 1996 Feb;70(2):762-77. doi: 10.1016/S0006-3495(96)79616-9.
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.
离子偶联转运体由一种不同于当代交替访问模式的模型进行模拟。该模型始于源自多离子孔的概念，假定底物（无机离子和小分子有机物）在以下两种情况间跳跃：a）溶液与结合位点之间；b）单排孔内的结合位点之间。任何两个底物都不能同时占据同一位置。跳跃的速率常数可通过以下两种方式提高：a）当两个位点中的底物相互吸引进入它们之间的空位时；b）当相邻位点中的底物相互排斥时。带电底物的跳跃速率常数也会受到膜电场的影响。对于一个三位点模型，模拟退火产生的参数能够拟合γ-氨基丁酸转运体GAT1的通量偶联、转运相关电流以及电荷移动的稳态测量值。该模型随后也解释了一些GAT1的动力学数据。该模型还产生了描述大鼠5-羟色胺转运体和兔钠-葡萄糖转运体可用数据的参数。模拟结果表明，偶联通量和离子转运的其他方面可以用一个包含局部底物-底物相互作用但无明确全局构象变化的模型来解释。
