that Asp237-Lys358 and Asp240-Lys319 interact 
functionally, and it is reasonable to suggest that both 
pairs of residues may be in close proximity. Thus 
putative helix VII (Asp237 and Asp240) may neigh- 
bor helices X (Lys319) and XI (Lys358) in the ter- 
tiary structure of the permease. 
Dr. Kaback is also Professor of Physiology and 
of Microbiology and Molecular Genetics and a 
member of the Molecular Biology Institute at the 
University of California, Los Angeles. 
Books and Chapters of Books 
Bibi, E., and Kaback, H.R. 1992. Recent studies on 
the lactose permease of Escherichia coli. In Mo- 
lecular Mechanisms of Transport (Quagliar- 
iello, E., and Palmieri, F., Eds.). New York: Else- 
vier Science, pp 175-179- 
Kaback, H.R. 1992. Beta-galactoside transport in 
Escherichia coli: the ins and outs of lactose per- 
mease. In Dynamics of Membrane Assembly 
(Op den Kamp, J.A.F., Ed.). New York: Springer- 
Verlag, vol H63, pp 293-308. {NATO AS! Se- 
ries.) 
Articles 
Bibi, E., and Kaback, H.R. 1992. Functional com- 
plementation of internal deletion mutants in the 
lactose permease of Escherichia coli. Proc Natl 
Acad Sci USA 89:1524-1528. 
Bibi, E., Stearns, S.M., and Kaback, H.R. 1992. 
The N-terminal 22 amino acid residues in the lac- 
tose permease of Escherichia coli are not obliga- 
tory for membrane insertion or transport activity. 
Proc Natl Acad Sci USA 89:3180-3184. 
Gros, P., Talbot, F., Tang-Wai, D., Bibi, E., and Ka- 
back, H.R. 1992. Lipophilic cations: a group of 
model substrates for the multidrug-resistance 
transporter. Biochemistry 31:1992-1998. 
Kaback, H.R. 1992. In and out and up and down 
with the lactose permease of Escherichia coli. Int 
Rev Cytol 137:97-125. 
Kaback, H.R. 1992. The lactose permease of Esche- 
richia coli: a paradigm for membrane transport 
proteins. Biochim Biopbys Acta 1101:21 0-2 13. 
McKenna, E., Hardy, D., and Kaback, H.R. 1992. 
Evidence that the final turn of the last transmem- 
brane helix in the lactose permease is required for 
folding. /fi/o/ Chem 261.6411-641 A. 
Pourcher, T., Bassilana, M., Sarkar, H.K., Kaback, 
H.R., and Leblanc, G. 1992. Melibiose permease 
of Escherichia coli: mutation of histidine-94 
alters expression and stability rather than catalytic 
activity. Biochemistry 31:5225-5231. 
van Iwaarden, P.R., Pastore, J.C., Konings, W.N., 
and Kaback, H.R. 1991 . Construction of a func- 
tional lactose permease devoid of cysteine resi- 
dues. Biochemistry 30:9595-9600. 
PROTEIN FOLDING AND MACROMOLECULAR RECOGNITION 
Peter S. Kim, Ph.D., Assistant Investigator 
Dr. Kim and his colleagues are interested in un- 
derstanding protein folding and macromolecular 
recognition. The laboratory is also using peptide 
and protein design to test and improve the knowl- 
edge base in folding and recognition. 
Protein Folding 
The mechanism of information transfer from one 
to three dimensions is a major unsolved problem in 
molecular biology. Much of the laboratory's work in 
protein folding is centered on bovine pancreatic 
trypsin inhibitor (BPTI), arguably the most thor- 
oughly characterized protein in biophysical terms. 
The native structure of BPTI is stabilized by three 
disulfide bonds. Following the pioneering studies of 
Dr. Thomas E. Creighton (European Molecular Biol- 
ogy Laboratory), Dr. Kim and his colleagues have 
determined the oxidative folding pathway for BPTI. 
Recent work has focused on characterization of 
early stages in this pathway and on determining the 
folding pathway for pro-BPTI. 
Three approaches are being used to obtain struc- 
tural information about BPTI-folding intermediates. 
First, peptide models for the early folding interme- 
diates are designed and studied. These models indi- 
cate that subdomains of native structure are stable 
in isolation. Second, recombinant models for the di- 
sulfide-bonded intermediates are made by replacing 
some of the cysteine residues with alanine. One vari- 
ant containing only a single disulfide bond is folded 
completely into a native BPTI structure and offers a 
new system for studies of protein folding. Third, the 
dynamic properties of BPTI variants containing a 
subset of disulfide bonds are being studied by mea- 
CELL BIOLOGY AND REGULATION 77 
