Most cell surface proteins are anchored to the cell bilayer by hydrophobic membrane-spanning domains. Recently it has been shown that a small class of molecules are attached to cell surfaces via a phosphatidylinositol moiety covalently linked to the C-terminus of the mature processed polypeptide. The molecular signals that identify a polypeptide for phosphatidylinositol (PI) attachment have not been well defined in any system, but are thought to reside in the C-terminus of the primary translation product. We report that all the signals responsible for PI anchoring of Qa-2 Ag are confined to the 36 C-terminal residues of the precursor proteins. To investigate further the features that signal cleavage and PI addition, we have studied mutants of two closely related murine class I MHC molecules: the PI-linked Ag, Q9b, from the Qa-2 Ag family, and the integral membrane transplantation antigen, H-2L(d). The addition of 15 amino acids to the three residue long cytoplasmic domain of Q9b or the mutation of Asp295 found in its C-terminal hydrophobic domain to Val converts this molecule into an integral membrane protein. However, the introduction of a short three residue cytoplasmic tail and Asp295 into the transmembrane domain of H-2L(d) does not convert this molecule to a PI-linked one. The results of these analyses suggest that the PI-processing signals may depend on overall conformation, hydrophobicity, and length of the C-terminal domain of the precursor protein. In addition these data indicate that PI anchoring of class I Ag requires more than two mutational steps and may have been selected during the evolution.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1990|
ASJC Scopus subject areas
- Immunology and Allergy