The laboratory of Assistant Investigator Robert O. 
Fox, Ph.D. (Yale University) has investigated the 
role of the amino acid sequence in determining the 
folding pathways and the final, detailed three-di- 
mensional structure of globular protein molecules. 
The laboratory has combined the methods of x-ray 
crystallography, NMR spectroscopy, and molecular 
=^ genetics to investigate how the sequence deter- 
mines turn and loop structures in immunoglobulin 
molecules and certain enzyme molecules, such as 
staphylococcal nuclease. In a genetic analysis of a 
P-turn in the nuclease, point mutations have been 
identified that transform a P-turn structure from 
one ideal type to another, while maintaining the 
globular protein structure. Thus a (J-turn element 
was transplanted from one protein to another, 
maintaining the local three-dimensional structure 
of the turn. The crystal structure of a Fab fragment 
has also been solved; this has suggested a struc- 
tural mechanism by which somatic mutations may 
modulate Fab-hapten affinity. 
The laboratory of Investigator Don C. Wiley, 
Ph.D. (Harvard College) continues to study 
the structure and function of cell and viral surface 
molecules. They have determined the structure of 
a complex between an influenza viral protein and a 
component of its cellular receptor. This should fa- 
cilitate the design of drugs to inhibit the virus from 
binding to cells. Using recombinant DNA methods, 
Dr. Wiley and his colleagues have also studied the 
membrane fusion mechanism by which viruses 
enter cells. Other studies determined the three- 
dimensional structure of the human histocompati- 
bility antigen, which is found on all human cells. 
The function of this protein during the immune re- 
sponse to viral infections and in the rejection of tis- 
sue transplantation is now being studied. 
The research of Investigator Stephen C. Harrison, 
Ph.D. (Harvard College) and his colleagues involves 
the elucidation of the detailed three-dimensional 
molecular structures of assemblies such as viruses, 
protein/DNA complexes, and cell-surface receptors. 
Such structural information is essential for under- 
standing how viruses assemble, how the expression 
of genes is selectively activated or repressed, and 
how viruses and other ligands are taken up by cells. 
During the last year the structure of SV40, a DNA 
tumor virus, has been determined. This is the larg- 
est virus to be visualized in such detail. Progress 
has also been made in understanding how regula- 
tory proteins of two different types recognize their 
specific DNA-binding sites. 
The laboratory of Assistant Investigator Sherry L. 
Mowbray, Ph.D. (University of Texas Southwestern 
Medical Center at Dallas) is studying receptors and 
membrane proteins. Mutants of a membrane pro- 
tein for bacterial chemotaxis have been used to ex- 
plore models for transmembrane signaling. Three 
soluble receptors for chemotaxis and transport are 
being studied by x-ray crystallography, with the aim 
of learning about the activation of receptor pro- 
teins and the transfer of signal information be- 
tween proteins. The leader peptidase of Es- 
cherichia coli is also being studied to help outline 
the events involved in the transfer of proteins 
across membranes. 
The research of Associate Investigator Carl O. 
Pabo, Ph.D. (The Johns Hopkins University) and his 
colleagues has focused on the structure and design 
of proteins that regulate gene expression. The labo- 
ratory is attempting to understand how proteins 
recognize specific sites on double-stranded DNA 
and how the bound proteins regulate gene expres- 
sion. Dr. Pabo's research has used a high-resolution 
crystal structure of the X repressor-operator com- 
plex as the basis for continued genetic and struc- 
tural analysis of repressor-operator interactions. 
Crystallographic studies of other repressors and re- 
pressor-operator complexes are in progress, and 
software is being developed for the general analysis 
and design of DNA-binding proteins. 
In the laboratory of Investigator Florante A. 
Quiocho, Ph.D. (Baylor College of Medicine), struc- 
tural analysis continues to reveal basic features of 
protein-Iigand interactions that are fundamental to 
o 
biological specificity and function. A 3 5 A resolu- 
tion electron density of the enzyme adenosine de- 
aminase has been calculated, providing an initial 
look at the structure of this key enzyme in normal 
immune system development. Site-directed muta- 
genesis and binding studies, coupled with x-ray 
analyses of binding proteins, provide insight into a 
variety of ligand recognitions. Crystals of an anti- 
body against gpl20, the coat protein of the human 
immunodeficiency virus (HIV), are of scientific and 
medical interest, as they promise to illuminate the 
structure of a possible antibody-binding site on the 
AIDS virus. The well-refined high-resolution struc- 
ture of calmodulin allows understanding of its in- 
teractions with calcium and its target enzymes. 
Protein molecules act both as regulators and tar- 
gets of regulation in biological processes. The labo- 
ratory of Assistant Investigator Stephen R. Sprang, 
Ph.D. (University of Texas Southwestern Medical 
Center at Dallas) has focused on the allosteric en- 
zyme glycogen phosphorylase, which is regulated 
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