Nature Structural Biology
3, 141 - 148 (1996)
doi:10.1038/nsb0296-141
Exploring the allowed sequence space of a membrane proteinJuan Wen1, Xing Chen1
& James U. Bowie1
1Department of Chemistry and Biochemistry and UCLA-DOE Laboratory of Structural Biology and Molecular Medicine University of California, Los Angeles 405 Hilgard Av., Los Angeles, California 90095-1570, USA We present a comprehensive view of the tolerance of a membrane protein to sequence substitution. We find that the protein, diacylglycerol kinase from Escherichia coli, is extremely tolerant to sequence changes with three-quarters of the residues tolerating non-conservative changes. The conserved residues are distributed with approximately the same frequency in the soluble and transmembrane portions of the protein, but the most critical active-site residues appear to reside in the second cytoplasmic domain. It is remarkable that a unique structure of the membrane embedded portion of the protein can be encoded by a sequence that is so tolerant to substitution.
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