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Please use this identifier to cite or link to this item: http://hdl.handle.net/10209/211

Title: RCK Domain Model of Calcium Activation in BK Channels
Authors: Pico, Alexander R.
Keywords: potassium ion channels
BK channels
calcium ion
RCK domains
Issue Date: 2003
Abstract: Potassium ion channels are ubiquitously expressed from bacteria to mammals where they are involved in various processes ranging from the regulation of osmotic pressure in a single cell to the electrical response in muscle fibers to the generation of action potentials in neurons. The B K channel family (BK for Big K+ conductance) is an interesting subfamily of K+ channels responsive to both membrane voltage and intracellular calcium ion. The unique, high-affinity Ca2+ sensitivity of B K channels is critical to their physiological function in various cell types. The mechanism by which Ca2+ activates B K channel gating, however, is not well understood. Here we present a structure-based approach to the study of B K channels with the goal of providing a structural and functional model of the Ca2+-activation mechanism. Sequence analysis of BK channel C-terminal domains and domains from prokaryotic homologs reveals the conservation of unique positions defining a novel regulatory domain associated with K conduction, the R C K domain. Crystal structures of R C K domains from prokaryotic sources relate the conservation of sequence to the structure, assembly and function of these domains. W e propose a hypothetical model for the structure and function of the Cterminal domains of B K as a set of R C K domains that conduct the Ca -activation mechanism. The features and constraints predicted by the R C K domain model are tested by the electrophysiological assay of a variety of human B K constructs. The results support a domain structure and assembly consistent with the proposed model for the B K C-terminus. In addition, the results identify residues and regions involved in Ca + activation: the Ca2+-binding event and the transduction of the binding energy through protein conformational changes to the channel domain. The R C K domain model thus provides a framework for the study of Ca2+ activation in B K channels.
Description: A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
RU Department Name: MacKinnon Laboratory
Appears in Collections:Student Theses

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