The full-length cDNA sequences of three variable surface glycoproteins from bloodstream forms of Trypanosoma congolense have been determined. They encode preproteins of 429, 449, and 428 amino acids. These proteins contain the typical N-terminal leader sequences of secreted eukaryotic proteins, and display hydrophobic amino acids at their C-termini characteristic of variable surface glycoproteins ; these leader sequences serve as transient membrane anchors after protein synthesis. By performing sequence comparisons of all currently known variable surface glycoproteins from 7: congolense, several conserved elements could be identified. These elements included positional conservation of most of the cysteine residues, conservation of the flanking sequences surrounding these cysteine residues, clustering of proline residues near the C-termini, and a hydrophobic heptad motif near the end of the N-terminal domains. The N-terminal domains seem to be closely related to the B domains of Trypanosoma brucei variable surface glycoproteins, whereas the C domains have up to now only been identified in 7: congolense variable surface glycoproteins. The data suggest that 7: congolense variable surface glycoproteins, despite low sequence similarities, could have conserved tertiary structures.African trypanosomes evade the immune system of their mammalian host by antigenic variation caused by rapidly switching the expression of the major surface glycoprotein or variable surface glycoprotein (VSG) genes [l]. Each organism has approximately one thousand different VSG genes [2], many of which can be expressed [3]. Usually, however, only one VSG gene is expressed at a time.VSG molecules form a homogeneous monolayer on the surface of bloodstream trypanosomes protecting underlying plasma membrane constituents from the humoral immune response. The variable antigenic determinants do not interfere with VSG packing into the protecting surface coat. Therefore, it is assumed that common structural features exist in antigenically differing VSGs that should be detectable in the DNA or protein sequences.To date, approximately 20-30 complete or partial amino acid sequences are known for antigenically distinct VSG from the Trypanosoma brucei group [4 -61. From Trypanosoma congolense only two complete amino acid sequences have been described for bloodstream VSG [7], and two additional sequences have been described for metacyclic VSG [8]. All VSG display N-terminal signal peptides and C-termi- Note. The novel sequence data published here have been submitted to the EMBL sequence data bank(s) and are available under accession number(s) X79399, X79400, X79401 for BENat 1-VSG, BENat 1.2-VSG and BENat 1.3-BSG mRNAs, respectively. nal hydrophobic amino acids which are absent in the mature proteins. Based primarily on conserved cysteine motifs, I ? brucei VSG have been grouped into several subfamilies [6]. The two 7: congolense VSG included in this analysis resemble N-terminal domain type B of 7: brucei VSG. The sequence similarity of VSG is low, even betw...