Construction of a Physical Model of a Voltage‐Dependent Potassium Ion Channel

Abstract

A partnership between students and Roderick MacKinnon enabled the Friends Seminary SMART Team (Students Modeling A Research Topic) to explore the structure and function of a chimaeric voltage‐gated K+ channel (Kvc) and to build a 3D physical model of its open conformation.Kvc are located along membranes of neurons and help repolarize the cells by allowing K+ to enter. The homo‐tetrameric Kvc we modeled consists of sensors that surround the pore helices, which form the central pore through which the K+ flows. On one end of the pore is a selectivity filter, which ensures that only K+ enter, and on the other end is the gate, which is either open or closed depending on the voltage around the membrane.A cleft in the sensor enables the paddle, a region of the sensor rich in positively charged residues, to monitor the separation charge across the membrane. In Kvc's open conformation, the paddle is attracted to the negatively charged extracellular fluid. After enough K+ flows out, the fluid around the paddle becomes more positively charged and repels the paddle to the other side of the membrane. This movement shifts the position of the S4‐S5 linker, which connects the sensor to the pore helices. The movement of the S4‐S5 linker in turn pushes the gate of the Kvc closed. When the intracellular fluid becomes more positively charged, Kvc returns to its open conformation. Supported by a grant from the HHMI Pre‐College Science Education Program.