conserved CCG triplet at each end of the site 
through contacts to bases in the major groove. Nu- 
clear magnetic resonance (NMR) studies show that 
this module is the only part of the 1-65 fragment 
that is folded when free in solution. The polypep- 
tide-chain backbone of the module has a remarkable 
internal dyad, but the amino acid sequence only re- 
flects the repeat in the position of Zn-liganding cys- 
teine residues. 
Dimer contacts in the complex are provided by a 
short, coiled coil dimerization module (residues 
50-65). This dimer surface is known to be aug- 
mented when additional residues are present. Re- 
cently grown crystals of a longer fragment from the 
related PPRl regulatory protein should reveal a 
more complete dimerization element. A segment of 
extended polypeptide chain links the recognition 
module to the dimerization element and specifies 
the length of the site. The relatively open structure 
of the complex would allow another protein to bind 
coordinately with GAL4. (The GAL4 project is sup- 
ported by a grant from the National Institutes of 
Health.) 
Dr. Harrison is also Professor of Biochemistry 
and Molecular Biology and Research Associate in 
the Laboratory of Molecular Medicine at the Chil- 
dren 's Hospital, Boston. 
Articles 
Baleja, J.D., Marmorstein, R., Harrison, S.C., and 
Wagner, G. 1992. Solution structure of the DNA- 
binding domain of Cd2-GAL4 from 5. cerevisiae. 
Nature 356:450-453. 
Harrison, S.C. 1992. Viruses. Curr Opin Struct 
Biol 2:295-299. 
Harrison, S.C, Strong, R.K., Schlesinger, S., and 
Schlesinger, M.J. 1992. Crystallization of Sindbis 
virus and its nucleocapsid. / Mo/ Biol 226:177- 
180. 
Liddington, R.C., Yan, Y., Moulai, J., Sahli, R., Ben- 
jamin, R.L., and Harrison, S.C. 1991. Structure 
of simian virus 40 at 3.8-A resolution. Nature 
356:408-414. 
Marmorstein, R., Carey, M., Ptashne, M., and Harri- 
son, S.C. 1992. DNA recognition by GAL4: struc- 
ture of a protein-DNA complex. Nature 
356:408-414. 
Moebius, U., Clayton, L.K., Abraham, S., Harrison, 
S.C, and Reinherz, E.L. 1992. The human immu- 
nodeficiency virus gpl20 binding site on CD4: 
delineation by quantitative equilibrium and ki- 
netic binding studies of mutants in conjunction 
with a high-resolution CD4 atomic structure. / 
Exp Med 176:507-517. 
STRUCTURAL STUDIES ON BIOLOGICAL MACROMOLECULES 
Wayne A. Hendrickson, Ph.D., Investigator 
Dr. Hendrickson and his co-workers study the 
structure and biological action of macromolecules, 
using diffraction analysis and other biochemical and 
biophysical methods as their principal research 
tools. They combine specific structural studies on 
important biological problems with methodology 
development aimed at facilitating their investiga- 
tions. The methodology work features synchrotron 
radiation, diffraction methods, and computational 
crystallography. The main biological themes con- 
cern cell surface interactions, genetic replication, 
carbohydrate-mediated recognition, and oxygen 
transport. The studies are also directed at general 
principles of protein structure, dynamics, and 
assembly. 
Cellular Signal Transduction 
The responses of cells to their environment obvi- 
ously involve molecular interactions at their cell 
surfaces, and many of these events generate signals 
that traverse the cell membrane. Crystallographic 
studies on extracellular receptor fragments and on 
intracellular kinase fragments and other transducing 
factors are beginning to elucidate some of the mo- 
lecular principles governing these processes. Dur- 
ing the past year, efforts have continued in the Hen- 
drickson laboratory on immune system receptors, 
on growth factors and their receptors, and on pro- 
tein kinases; studies have also been initiated on cell 
adhesion molecules. 
Regarding CD4, a second crystal form of the 
D1D2 fragment has been solved; crystals have been 
grown from the first of a series of mutant proteins 
(with Dr. Ray Sweet, SmithKline Beecham); and the 
CD4 :class II interaction is being studied in structure- 
guided mutational studies (with Dr. Rafick Sekaly, 
Clinical Research Institute of Montreal). The crystal 
structure of an extracellular fragment of CD8 has 
STRUCTURAL BIOLOGY 473 
