Roderick MacKinnon, M.D.


Our research aims to understand the molecular mechanisms of a class of integral membrane proteins known as ion channels. By catalyzing the rapid and selective flow of inorganic ions across cell membranes, these proteins generate electrical signals in cells. Among their many biological functions, ion channels control the pace of the heart, regulate hormone secretion and generate the electrical impulses underlying information transfer in the nervous system. Central questions in the field of mechanistic ion channel studies include: How do their pores discriminate between very similar ions such as those of sodium and potassium, and how does neurotransmitter binding or a change in a cell's membrane voltage control the gating (opening and closing) process?We take a multidisciplinary approach to answer these questions. We study the activity or function of ion channels through patch-recording, a technique that allows one to monitor the behavior of a single protein molecule in real-time. We investigate the structure of ion channels using diffraction methods. Currently, the structure effort consists of three components: (a) work on high-level expression and purification of ion channels, (b) development of methods for growing two dimensional crystals (for electron microscopy studies) using small quantities of channel protein and (c) X-ray crystallographic studies of ion channel domains and soluble regulatory proteins that bind to ion channels.

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