Chapter 7 Attachment of a GPI Anchor to Protein

Abstract

I. Abstract Proteins destined to receive a GPI anchor are synthesized with two signal sequences: an N‐terminal signal sequence that targets the preproprotein to the endoplasmic reticulum (ER), and a C‐terminal signal sequence that directs the attachment of a preassembled GPI anchor. The attachment of a GPI anchor to the protein's C‐terminus occurs via a transamidation reaction that is catalyzed by the GPI transamidase (GPIT), a membrane‐bound, penta‐subunit enzyme complex. The different GPIT subunits are conserved from protozoa to yeast to mammals either by sequence or membrane topology. While GPI8 has been shown to be the catalytic subunit, the function of the other proteins within the GPIT complex is still unclear. PIG‐U and GAA1 have been proposed to be involved in recognizing and binding of the GPI, while comparison of PIG‐T with proteins of known 3D structure predicts that it forms a funnel‐like structure, leading to speculations about a role of this subunit in gating the proprotein to the GPI anchor for transamidation. Subjects for future research include testing the involvement of these subunits in recognition and binding of the GPI anchor and/or the protein substrate, as well as structural analysis of GPIT.