Schematic representation of the protein chain of a typical VSG. The polypeptide is composed of some 500 amino acids. The N-terminus contains a signal peptide for transport through the ER and to the plasma membrane, which is cleaved off from the mature protein. The variable region is different for each VSG and shows little or no identity with other VSGs. Towards the C-treminal part the polypeptide chain is better conserved and this part is called the homology region. The hydrophobic tail contains a recognition signal for attachment to the glycolipid anchor (see below). When the anchor is attached the last 20 amino acids are cleaved off.
Structure
of the glycolipid anchor for VSG. (modified from Dr. G.A.M.
Cross)
The variable surface glycoprotein (VSG) is attached to the membrane via a glycolipid anchor consisting of ethanolamine, a glycan structure containing several mannose moieties, a glucosamine and a phosphoinositol that is linked to a 1,2-dimyristoylglycerol burried in the plasma membrane. The glycolipid moiety is the so-called cross-reacting determinant (CRD) that is recognized by antibodies that react with all VSG variants, but only when the VSG has been released from the membrane. Membrane bound VSG is not recognized by anti-CRD antibodies. This release of VSG is catalyzed by the activation of a trypanosome-specific phospholipase C supposed to be present on the inner face of the plasma membrane. It is not known how this enzyme may cleave the phosphoester bond on the other side of the membrane.
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