Implications of conserved structural motifs in disparate trypanosome surface proteins.
Evasion of the host immune system by Trypanosoma brucei is dependent on the sequential expression of individual genes encoding antigenically distinct variant surface glycoproteins (VSG). VSGs are antigenically distinct due to extensive differences in primary sequence; the only obvious conserved feature in the primary sequence is the location of cysteines that form disulphide bridges. Despite this difference, it is believed that VSGs have a conserved tertiary structure which could explain how a range of VSGs with different primary sequences can perform the same apparent function of producing a monolayer barrier that prevents the host antibodies from recognising other cell surface proteins. The main feature of the VSG tertiary structure is two long alpha-helices per monomer that are perpendicular to the cell surface and define the elongated shape of the VSG. The alpha-helices can be identified in the primary sequence by heptad analysis. Here, we briefly review the current understanding of VSG structure and discuss the fact that the cysteine residues and the heptads are conserved in some non-VSG surface proteins from T. brucei, providing strong evidence that these share a similar tertiary structure. These findings suggest that this master structure has evolved to facilitate a range of functions and has implications for understanding the architecture of the trypanosome cell surface and the origins of antigenic variation.
University of Cambridge, Department of Biochemistry, UK. mc115@mole.bio.cam.ac.uk
M
M
Carrington
J
J
Boothroyd
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D017124:Conserved Sequence; D003545:Cysteine / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D015394:Molecular Structure; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
D014643:Variant Surface Glycoproteins, Trypanosoma; D003545:Cysteine