Nature 325, 84 - 86 (01 January 1987); doi:10.1038/325084a0

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

P. Metcalf, M. Blum, D. Freymann, M. Turner^* & D. C. Wiley

Department of Biochemistry and Molecular Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
^* Merck, Sharp and Dohme Research Laboratories, PO Box 2000, Rahway, New Jersey 07065, USA

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 -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.

References

1.	Cross, G. A. M. Phil. Trans. R. Soc. Lond. B307, 3−12 (1984).
2.	Turner, M. J. Phil. Trans. R. Soc. Lond. B307, 27−40 (1984).
3.	Van der Ploeg, L. H. T. et al. Nucleic Acids Res. 10, 5905−5923 (1982). | PubMed | ChemPort |
4.	Freymann, D., Metcalf, P., Turner, M. J. & Wiley, D. Natute 311, 167−169 (1984). | ChemPort |
5.	Cardoso de Almeida, M. L. & Turner, M. J. Nature 302, 349−352 (1983). | Article | PubMed | ChemPort |
6.	Ferguson, M. A. J. & Cross, J. A. M. J. biol. Chem. 259, 3011−3015 (1984). | PubMed | ISI | ChemPort |
7.	Ferguson, M. A. J., Haldar, K. & Cross, J. A. M. J. biol. Chem. 260, 4963−4968 (1985). | PubMed | ISI | ChemPort |
8.	Auffret, C. A. & Turner, M. J. Biochem. J. 193, 647−650 (1981). | PubMed | ISI | ChemPort |
9.	Gurnet, A. M., Raper, J. & Turner, M. J. Molec. biochem. Parasitol. 18, 141−153 (1986).
10.	Johnson, J. G. & Cross, G. A. M. Biochem. J. 178, 689−697 (1979). | PubMed | ISI | ChemPort |
11.	Holder, A. A. & Cross, G. A. M. Molec. biochem. Parasitol. 2, 135−150 (1981). | ChemPort |
12.	Rice-Ficht, A. C., Chen, K. K. & Donelson, J. E. Nature 294, 53−57 (1981). | Article | ChemPort |
13.	Cohen, C. et al. Nature 311, 169−171 (1984). | Article | PubMed | ChemPort |
14.	Olafson, R. W. et al. Molec. biochem. Parasitol. 12, 287−298 (1984). | ChemPort |
15.	Lalor, T. M. et al. Proc. natn. Acad. Sci. U.S.A. 81, 998−1002 (1984). | ChemPort |
16.	Cross, G. A. M., J. Cell Biochem. 24, 79−90 (1983).
17.	Durbin, R. M. et al. Science 232, 1127−1132 (1986). | PubMed | ChemPort |
18.	Blum, M., Metcalf, P., Harrison, S. C. & Wiley, D. C. J. appl. Cryst. (in the press).
19.	Fox, G. C. & Holmes, K. C., Acta cryst. 20, 886−891 (1966). | Article | ChemPort |
20.	Dickerson, R. E., Weinzierl, J. E. & Palmer, R. A. Acta cryst. B24, 997−1003 (1968).
21.	Wang, B. C. Meth. Enzym. 115, 90−112 (1985). | PubMed | ChemPort |
22.	Turner, M. J., Biochem. Soc. Symp. 49, 169−181 (1984). | PubMed | ChemPort |
23.	Turner, M. J., Annls Inst. Pasteur, Paris (Immunol.) 136C, 41−49 (1985). | ChemPort |
24.	Metcalf, P. et al. (manuscript in preparation).