Efficient Glycosylphosphatidylinositol (GPI) Modification of Membrane Proteins Requires a C-terminal Anchoring Signal of Marginal Hydrophobicity
2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 20, 16399-16409 p.Article in journal (Refereed) Published
Many plasma membrane proteins are anchored to the membrane via a C-terminal glycosylphosphatidylinositol (GPI) moiety. The GPI anchor is attached to the protein in the endoplasmic reticulum by transamidation, a reaction in which a C-terminal GPI-attachment signal is cleaved off concomitantly with addition of the GPI moiety. GPI-attachment signals are poorly conserved on the sequence level but are all composed of a polar segment that includes the GPI-attachment site followed by a hydrophobic segment located at the very C terminus of the protein. Here, we show that efficient GPI modification requires that the hydrophobicity of the C-terminal segment is marginal: less hydrophobic than type II transmembrane anchors and more hydrophobic than the most hydrophobic segments found in secreted proteins. We further show that the GPI-attachment signal can be modified by the transamidase irrespective of whether it is first released into the lumen of the endoplasmic reticulum or is retained in the endoplasmic reticulum membrane.
Place, publisher, year, edition, pages
2012. Vol. 287, no 20, 16399-16409 p.
Endoplasmic Reticulum (ER), Glycosylphosphatidylinositol Anchors, Membrane Proteins, Post-translational Modification, Protein Translocation, Transmembrane Helix
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-80109DOI: 10.1074/jbc.M112.350009ISI: 000304030900031OAI: oai:DiVA.org:su-80109DiVA: diva2:553387
FunderEU, European Research CouncilSwedish Foundation for Strategic Research Swedish Research Council