Structural studies of a human gamma 3 myeloma protein (Goe) that binds staph protein A.

The partial amino acid sequence of the Fc region of an unusual monoclonal immunoglobulin molecule (Goe), which had the allotypic markers Gm (b0, b3, b5, s, t, v), rarely encountered in Caucasians, was determined. Protein Goe was previously shown to belong to the gamma 3 subclass by antigenic typing, to possess a gamma 3-like hinge region and a gamma 1-like carboxy-terminal octadecapeptide, and to bind to staphylococcal protein A. The sequence of protein Goe resembled that of gamma 3 molecules except for the presence of tyrosine at position 296, alanine at position 339, and histidine and tyrosine at positions 435 and 436. It is of interest that histidine 435 appears to play an important role in binding to Staph protein A. Since tyrosine and phenylalanine at 296 and 300 are typical of G3m(g) molecules, whereas protein Goe is G3m(g-), this may correspond to the non-b1 allotypic marker. Of the numerous explanations to account for these findings, the most likely possibilities are that protein Goe is either a hybrid molecule or the product of a germ line gene representing the G3m s allotype, which is rare in Caucasians and common in Mongoloid populations. Support for the latter alternative is provided by the isolation from normal serum of a small amount of a protein having many of the properties of protein Goe.