Abstract
CELL-SURFACE proteins are associated with the lipid bilayer either as membrane-spanning molecules or as glycosyl phos-phatidylinositol (GPtdIns)-linked proteins. Proteins destined for GPtdIns anchoring are synthesized as precursors with a hydrophobic C-terminal transmembrane domain, which is removed during the processing of these proteins in the endoplasmic reticulum (ref. 1). We have investigated the structural requirements for GPtdIns anchoring through the study of two closely related pro-teins which exhibit alternative membrane attachment. The IgG Fc receptor, FcγRIII, is GPtdIns-linked on neurophils (III-1)2–4 whereas on natural killer (NK) cells and macrophages it is found as a transmembrane-anchored molecule (III-2)4,5, able to mediate antibody-dependent cellular cytotoxicity and phagocytosis6. At the primary structural level, the III-1 gene differs from that encoding III-2 by only nine nucleotide substitutions, which result in six amino-acid differences, and the absence of 21 amino acids at the C terminus4,5,7. We have analysed a series of III-1 and III-2 mutants in transient expression assays, and show that Ser 203 in the GPtdIns attachment domain is the dominant residue in deter-mining whether the molecule can be GPtdIns-anchored. As in the case of its murine homologue, FcγRIIα, surface expression of the III-2 molecule is dependent on co-expression of a second subunit, the γ chain of FɛRI. Our data also suggest that γ chain can associate with the III-1 precursor, preventing GPtdIns attachment, favouring instead a transmembrane form.
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Kurosaki, T., Ravetch, J. A single amino acid in the glycosyl phosphatidylinositol attachment domain determines the membrane topology of FcγRIII. Nature 342, 805–807 (1989). https://doi.org/10.1038/342805a0
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DOI: https://doi.org/10.1038/342805a0
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