It's hard. See:

J Mol Biol. 2005 May 6;348(3):777-87.
X-ray structure of a water-soluble analog of the membrane protein phospholamban: sequence determinants defining the topology of tetrameric and pentameric coiled
coils.
Slovic AM, Stayrook SE, North B, Degrado WF.

Slovic, A. M., Summa, C. M., Lear, J. D. & DeGrado,
W. F. (2002). Computational design of a water-soluble
analog of phospholamban. Protein Sci. 12, 337–348.

Li, H., Cocco, M. J., Steitz, T. A. & Engelman, D. E.
(2001). Conversion of phospholamban into a soluble
pentameric helical bundle. Biochemistry, 40,
6636–6645.

Frank, S., Kammerer, R. A., Hellstern, S., Pegoraro, S.,
Stetefeld, J., Lustig, A. et al. (2000). Toward a high resolution
structure of phospholamban: design of
soluble transmembrane domain mutants.
Biochemistry, 39, 6825–6831.

Tom


Daniel Jin wrote:
Hi,
I am wondering whether there is a way to turn a membrane protein with known crystal structure into a water soluble protein by systematic mutagenesis. I guess it should be doable if we introduce enough hydrophilic residues on the surface. Has anyone tested this crazy idea before? Thank you for your help.
Best,
Chen

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Thomas J. Magliery, Ph.D.
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Department of Chemistry
& Department of Biochemistry
The Ohio State University
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