consequent non-coplanarity distorts Watson-Crick 
hydrogen bonds, but certain sequences permit 
compensatory bifurcated hydrogen bonding. Such 
sequences at the center of the 434 operators ap- 
pear to create particularly good binding sites. The 
434 Cro protein imposes a similar but distinct con- 
formation when it binds specifically to DNA. The 
difference involves a shift in the sugar-phosphate 
backbone, around a nucleotide critical for the dis- 
tinction between Cro and repressor specificity, and 
it apparently results from differences in the identity 
or conformation of various residues contacting the 
DNA backbone, some of which lie outside the helix- 
turn-heltx element. Only by taking into account the 
different DNA conformations imposed by these pro- 
teins can their characteristic affinities be explained. 
Two proteins representing a different class of 
DNA-binding domains are now being studied. GAL4 
(an activator of transcription in yeast) contains one 
form of a so-called zinc finger, and Tfllla (a tran- 
scription factor for the 5S RNA gene in Xenopus) 
contains another. Crystals of the GAL4-binding do- 
main in complex with DNA and of the Tfllla-bind- 
ing region in complex with 5S RNA have recently 
been prepared. 
III. Receptors. 
The transferrin receptor (tfR) is a dimer of 90 
kDa transmembrane subunits. It transits an endocy- 
PUBLICATIONS 
totic pathway involving entry into low-pH endoso- 
mal compartments via coated pits and coated vesi- 
cles. Digestion of purified tfR with trypsin at neu- 
tral pH generates a soluble noncovalent dimer of 
70 kDa fragment subunits containing most of the 
extracellular sequence, including the transferrin- 
binding sites. Below pH 6, the 70 kDa fragment un- 
dergoes a conformational transition, leading to re- 
versible association of the dimers in solution. 
Nonliganded tfR in coated vesicles appears to un- 
dergo a similar association. These properties sug- 
gest that intracellular sorting events may involve 
conformational changes of the ectodomain in en- 
dosomal lumina. To explore this and other proper- 
ties of a "typical" receptor participating in the 
coated vesicle pathway. Dr. Harrison and his col- 
leagues have prepared crystals of the 70 kDa frag- 
ments. The crystals diffract to spacings of 3.5 A, and 
the structure determination is at a relatively ad- 
vanced stage. 
Crystallographic studies of CD4, the receptor for 
human immunodeficiency virus (HIV), are also in 
progress (in collaboration with scientists at Biogen 
and at the Dana-Farber Cancer Institute). Forms 
being studied include the complete extracellular 
part of the molecule and smaller fragments that still 
retain HIV-binding activity. 
Dr. Harrison is also Professor of Biochemistry and 
Molecular Biology at Harvard University. 
Books and Chapters of Books 
Harrison, S.C. 1989. Common features in the design of small RNA viruses. In Concepts in Viral Pathogenesis 
in. New York: Springer-Verlag, pp 3-19. 
Articles 
Aggarwal, A.K., Rodgers, D.W, Drottar, M., Ptashne, M., and Harrison, S.C. 1988. Recognition of a DNA opera- 
tor by the repressor of phage 434: a view at high resolution. Science 242:899-907. 
Koudelka, G.B., Harbury R, Harrison, S.C , and Ptashne, M. 1988. DNA twisting and the affinity of bacterio- 
phage 434 operator for bacteriophage 434 repressor. Proc Natl Acad Sci USA 85:4633-4637. 
Mondragon, A., Subbiah, S., Almo, S.C, Drottar, M., and Harrison, S.C. 1989. Structure of the amino-terminal 
domain of phage 434 repressor at 20 A resolution. JMol Biol 205:189-200. 
o 
Mondragon, A., Wolberger, C, and Harrison, S.C. 1989. Structure of phage 434 Cro protein at 2.35 A resolu- 
tion. /Mo/ 5/o/ 205:179-188. 
Turkewitz, A.P., and Harrison, S.C. 1989. Concentration of transferrin receptor in human placental coated 
vesicles. /Ce/Z^/o/ 108:2127-2135. 
Turkewitz, A.P, Schwartz, A.L., and Harrison, S.C 1988. A pH-dependent reversible conformational transition 
of the human transferrin receptor leads to self-association. J Biol Chem 263: 16309-16315. 
Continued 
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