".gamma. Subunit" of sodium-potassium-ATPase, a small, amphiphilic protein with a unique amino acid sequence

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Abstract
The ".gamma. subunit", or "proteolipid", of Na,K-ATPase is a small, membrane-bound protein that copurifies with the .alpha. and .beta. subunits of this enzyme. The importance of .gamma. in the function of Na,K-ATPase remains to be established, but some evidence indicates that it may be involved in forming a receptor site for cardiac glycosides. We have previously communicated [Reeves, A. S., Collins, J. H., and Schwartz, A. (1980) Biochem. Biophys. Res. Commun. 95, 1591-1598] the purification and amino acid composition of sheep kidney .gamma., and in this paper we present the first available sequence information on this protein. Although the amino terminus of .gamma. seems to be blocked and it is resistant to proteolytic cleavage, we have determined approximately half of its amino acid sequence. Our results indicate that .gamma. contains a total of 68 amino acid residues, with a calculated Mr of 7675. The sequenced portion appears to be at the carboxyl terminus of the polypeptide chain. The .gamma. sequence is unique, providing strong evidence for its homogeneity and establishing for the first time that it is not a breakdown product of the .alpha. or .beta. subunits. .gamma. is not a true proteolipid, but rather it is an amphiphilic protein with two distinct structural domains. The amino-terminal domain (residues 1-49) is very hydrophilic, with many charged amino acid side chains, and must be extracellular. This domain includes a concentrated segment of four aromatic residues which may be involved in glycoside binding. The carboxyl-terminal domain (residues 50-68) is hydrophobic and probably spans the cell membrane.