Document Type
Journal Article
Date of this Version
2-17-2004
Publication Source
Proceedings of the National Academy of Sciences of the United States of America
Volume
101
Issue
7
Start Page
1828
Last Page
1833
DOI
10.1073/pnas.0306417101
Abstract
Although the interiors of membrane and water-soluble proteins are similar in their physicochemical properties, membrane proteins differ in having larger fractions of hydrophobic residues on their exteriors. Thus, it should be possible to water-solubilize membrane proteins by mutating their lipid-contacting side chains to more polar groups. Here, a computational approach was used to generate water-soluble variants of the potassium channel KcsA. As a probe of the correctness of the fold, the proteins contain an agitoxin2 binding site from a mammalian homologue of the channel. The resulting proteins express in high yield inEscherichia coli and share the intended functional and structural properties with KcsA, including secondary structure, tetrameric quaternary structure, and tight specific binding to both agitoxin2 and a small molecule channel blocker.
Recommended Citation
Slovic, A. M., Kono, H., Lear, J. D., Saven, J. G., & DeGrado, W. F. (2004). Computational Design of Water-Soluble Analogues of the Potassium Channel KcsA. Proceedings of the National Academy of Sciences of the United States of America, 101 (7), 1828-1833. http://dx.doi.org/10.1073/pnas.0306417101
Date Posted: 07 December 2016
This document has been peer reviewed.