| | |
Summary: The Folding Landscape of an -Lytic Protease Variant
Reveals the Role of a Conserved -Hairpin in the
Development of Kinetic Stability
Stephanie M. E. Truhlar1
and David A. Agard1,2*
1
Graduate Program in Chemistry and Chemical Biology, University of California, San Francisco, San Francisco, California
2
Howard Hughes Medical Institute and the Department of Biochemistry and Biophysics, University of California, San
Francisco, San Francisco, California
ABSTRACT Most secreted bacterial proteases,
including -lytic protease ( LP), are synthesized
with covalently attached pro regions necessary for
their folding. The LP folding landscape revealed
that its pro region, a potent folding catalyst, is
required to circumvent an extremely large folding
free energy of activation that appears to be a conse-
quence of its unique unfolding transition. Remark-
ably, the LP native state is thermodynamically
unstable; a large unfolding free energy barrier is
|
