In 1971, “next to nothing was known about the organization of membrane proteins,” says S. Jonathan Singer (University of California, San Diego, CA). Singer had proposed that there were two kinds of membrane proteins— integral and peripheral—but the idea was, at the time, largely speculative (Singer, 1971). It was a collaborative study between Singer, his then graduate student Garth Nicolson, and Vincent Marchesi of the National Institutes of Health that provided strong evidence for the existence of peripheral proteins (Nicolson et al., 1971a).
Earlier work by Marchesi and Steers (1968) had shown that the protein spectrin was associated with the membranes of red blood cells. It could be isolated by mild treatments and behaved like a water-soluble protein. Some researchers thought spectrin was typical of membrane proteins in general. Singer's model, however, proposed that integral membrane proteins, which passed through the membrane, would be insoluble...
