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Principal Research Interests |
Protein Folding
The protein folding problem, namely how amino acid sequence determines the
three-dimensional structure of a protein, is not fully understood despite
many years of effort. We are addressing this problem in a variety of ways
in our laboratory: We study the conformational preferences of model peptides
in order to explore how local sequence guides folding. We are also carrying
out detailed studies of the in vitro folding of a predominantly β–sheet protein
with a very simple topology. Methods we use in all of our folding work include
circular dichroism, fluorescence,and nuclear
magnetic resonance.
Chaperones
We are also interested in how a protein folds in vivo. In recent years,
a class of proteins called molecular chaperones has been found to facilitate
protein folding in vivo. We are addressing several questions concerning
chaperones: How do they recognize and bind incompletely folded polypeptides?
Do different classes of chaperones bind to their substrates in distinct
ways? How do chaperones interact with their co-chaperones? Is the mechanism
of chaperone-mediated folding different from that of the isolated protein?
Signal sequences
Many proteins that are synthesized on cytoplasmic ribosomes are destined
to function in non-cytoplasmic locations. We are interested in how the
newly synthesized chain is directed to either extracellular or organellar
sites. We have extensively examined biophysical properties of signal
sequences, which facilitate the export of bacterial proteins, to elucidate
their mode of action in vivo. We are now studying the interaction of
signal sequences with proteins of the export pathway, including the bacterial
proteins SecA and Ffh.
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