Two variant surface glycoproteins of Trypanosoma Brucei of different sequence classes have similar 6 Å resolution X-ray structures

Abstract

Antigenic variation in the African trypanosome is mediated through changes in the composition of the surface coat^1,2. By controlling expression of the major surface protein, the variant surface glycoprotein (VSG), from a repertoire of perhaps 1,000 different genes³ the organisms exhibit a series of antigenically distinct coats and evade the host's immune system. We have determined the 6 Å resolution structure of a T. brucei variant surface glycoprotein, ILTat 1.24, using X-ray crystallography. The crystallized protein consists of the N-terminal two-thirds of the intact VSG which has a relative molecular mass (M_r) of 60,000 (60K). The structure, which includes a 90 Å long α-helical bundle, is strikingly similar to that of the N-terminal fragment of VSG MFTat 1.2 (ref. 4). Although most known VSG sequences show little similarity of primary sequence in the N-terminal domain, the similarity between the structure of a Class I (ILTat 1.24) and a Class II (MITat 1.2) VSG antigen suggests that VSGs may share a common tertiary structure.