A28, which has changes at 13 of the 16 most poly- 
morphic amino acid positions, has been deter- 
mined and refined to 2.6 A resolution. Because of 
its extensive polymorphism, A28 would appear to 
be a good model for the effect of polymorphism on 
class I molecules. The structure of A28 is similar to 
A2. The prominent cleft is similar and also contains 
extra density, presumably the image of a peptide or 
collection of peptides. The polymorphic substitu- 
tions result in significant changes in the character 
of the binding cleft. One particular region that is 
relatively flat in HLA-A2 has a deep pocket lined 
with two unneutralized carboxylate groups, sug- 
gesting a role in binding a positively charged por- 
tion of a foreign peptide. A significant peak of the 
extra density is found in this pocket. 
Crystals of the human class II histocompatibility 
antigen HLA-DRl have been grown in collaboration 
with Dr. Jack Strominger (Harvard University). It 
appears possible to add peptides to these crystals, 
which have been shown in the laboratory to bind 
to HLA-DRl. 
PUBLICATIONS 
Efforts to bind peptides to HLA-A2 are also in 
progress. 
III. Variable-Surface Glycoprotein. 
The structures of two variable-surface glycopro- 
teins from the membrane of the parasite Trypano- 
soma brucei have been determined to 2.8 A resolu- 
tion. The molecules lack statistically significant 
sequence homology, yet have extremely similar 
structures. 
IV Human Immunodeficiency Virus (HIV). 
In collaboration with Dr. Stephen C. Harrison 
(HHMI, Harvard University), Dr. Wiley has initiated 
studies on proteins from HIV and its cellular recep- 
tor. A number of crystal forms of CD4 have been 
obtained. 
Dr. Wiley is also Professor of Biochemistry and 
Biophysics at Harvard University. 
Articles 
Metcalf, E, Down, J.A., Turner, M.J., and Wiley, D.C. 1988. Crystallization of amino-terminal domains and do- 
main fragments of variant surface glycoproteins from Trypanosoma brucei brucei. J Biol Chem 
263:17030-17033. 
Ruigrok, R.WH., Aitken, A., Calder, L.J., Martin, S.R., Skehel, J.J., Wharton, S.A., Weis, W, and Wiley D.C. 
1988. Studies on the structure of the influenza virus haemagglutinin at the pH of membrane fusion./ Gen 
Virol 69:2785-2795. 
Wharton, S.A., Martin, S.R., Ruigrok, R.WH., Skehel, J.J., and Wiley D.C. 1988. Membrane fusion by peptide 
analogues of influenza virus haemagglutinin./ Gen Virol 69:1847-1857. 
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