resolution. (The studies of DRl are partially sup- 
ported by the National Institutes of Health through 
grants to Drs. Strominger and Gorga.) These studies 
should offer insight into the function of class II mol- 
ecules in regulating the production of immune sera. 
A number of studies on influenza virus continue 
in collaboration with Dr. John Skehel in London. In 
the past year the resolution of the studies has been 
increased from 3. OA to ~2.2Abya combination of 
flash freezing and the use of phosphor image plates 
and the CHESS Fl synchrotron beam line. The labora- 
tory has also begun characterizations of an inhibitor 
of virus-cell binding with 1,000-fold greater po- 
tency than sialic acid, the natural receptor. (Both 
the work on influenza virus and that of collaborators 
Drs. Jeremy Knowles and George Whitesides are 
supported by the National Institutes of Health.) 
Studies on trypanosome variant-surface glycopro- 
teins (VSGs) resulted this year in an analysis of two 
variant molecules with only 16% sequence homol- 
ogy but identical structure. A core of conserved 
amino acid residue type that appears to "hold" the 
structure together can be described. In some vari- 
ants this core appears to be buried by carbohydrate 
residues rather than protein. The study establishes 
that antigenic variation in trypanosomes is caused 
by sequence variation and not by gross structural 
alterations. It also argues that the different classes of 
VSGs constitute a protein superfamily rapidly evolv- 
ing within a single organism. (The trypanosome re- 
search is supported by the National Institutes of 
Health.) 
The National Institutes of Health also supported 
work on influenza C virus, gpl20 and gpl60 of 
HIV-1, and a low-pH, fusion-active conformation of 
the influenza A virus hemagglutinin. 
Dr. Wiley is also Professor of Biochemistry and 
Biophysics in the Department of Biochemistry and 
Molecular Biology at Harvard University and Re- 
search Associate in Medicine at the Children 's Hos- 
pital, Boston. 
Articles 
Carrington, M., Miller, N., Blum, M., Roditi, I., Wi- 
ley, D.C., and Turner, M. 1991- Variant specific 
glycoprotein of Trypanosoma brucei consists of 
two domains each having an independently con- 
served pattern of cysteine residues. / Mol Biol 
221:823-835. 
Garboczi, D.N., Hung, D.T., and Wiley, D.C. 1992. 
HLA-A2-peptide complexes: refolding and crystal- 
lization of molecules expressed in Escherichia 
coli and complexed with single antigenic pep- 
tides. Proc Natl Acad Sci USA 89:3429-3433- 
Glick, G.D., Toogood, P.L., Wiley, D.C, Skehel, J.J. , 
and Knowles, J.R. 1991- Ligand recognition by 
influenza virus. The binding of bivalent sialo- 
sides. f Biol Chem 266:23660-23669. 
Godley, L., Pfeifer, J., Steinauer, D., Ely, B., Shaw, 
G., Kaufmann, R., Suchanek, E., Pabo, C, Skehel, 
J.J., Wiley, D.C, and Wharton, S. 1992. Intro- 
duction of intersubunit disulfide bonds in the 
membrane-distal region of the influenza hemag- 
glutinin abolishes membrane fusion activity. Cell 
68:635-645. 
Gorga, J.C., Brown, J.H., Jardetzky, T., Wiley, 
D.C, and Strominger, J. L. 1991. Crystallization of 
HLA-DR antigens. Res Immunol 142:401-407. 
Gorga, J. C, Madden, D.R., Prendergast, J.K., Wiley, 
D.C, and Strominger, J.L. 1992. Crystallization 
and preliminary X-ray diffraction studies of the 
human major histocompatibility antigen HLA- 
B27. Proteins 12:87-90. 
Hanson, J.E., Sauter, N.K., Skehel, J.J., and Wiley, 
D.C. 1992. Proton nuclear magnetic resonance 
studies of the binding of sialosides to intact influ- 
enza virus. Virology 189:525-533. 
Jardetzky, T.S., Lane, W.S., Robinson, R.A., Madden, 
D.R., and Wiley, D.C. 1991. Identification of self 
peptides bound to purified HLA-B27. Nature 
353:326-329. 
Madden, D.R., Gorga, J. C, Strominger, J.L. , and Wi- 
ley, D.C. 1991. The structure of HLA-B27 reveals 
nonamer "self-peptides" bound in an extended 
conformation. Nature 353:321-325. 
Madden, D.R., and Wiley, D.C. 1992. Peptide bind- 
ing to the major histocompatibility complex mole- 
cules. Curr Biol 2:300-304. 
Parker, K.C, Silver, M.L., and Wiley D.C. 1992. An 
HLA-A2//32-microglobulin/peptide complex as- 
sembled from subunits expressed separately in 
Escherichia coli. Mol Immunol 29:371-378. 
Pollard, S R., Meier, W., Chow, P., Rosa, J.J., and 
Wiley, D.C. 1991. CD4-binding regions of hu- 
man immunodeficiency virus envelope glycopro- 
tein gpl 20 defined by proteolytic digestion. Proc 
Natl Acad Sci USA 88:11320-11324. 
Pollard, S.R., Rosa, M.D., Rosa, J.J. , and Wiley, D.C. 
1992. Truncated variants of gpl 20 bind CD4 
with high affinity and suggest a minimum CD4 
binding region. EMBO / 11:585-591. 
Sauter, N.K., Glick, G.D., Crowther, R.L., Park, S.-J., 
Eisen, M B., Skehel, J.J. , Knowles, J. R., and Wiley, 
D.C. 1992. Crystallographic detection of a sec- 
ond ligand binding site in influenza virus hemag- 
glutinin. Proc Natl Acad Sci USA 89:324-328. 
STRUCTURAL BIOLOGY 491 
