Artikel,
Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins.
Proc Natl Acad Sci U S A, 105 (49): 19241-6 (Dezember 2008)
Zusammenfassung
The energy landscape theory provides a general framework for
describing protein folding reactions. Because a large number of
studies, however, have focused on two-state proteins with single
well-defined folding pathways and without detectable intermediates,
the extent to which free energy landscapes are shaped up by
the native topology at the early stages of the folding process has
not been fully characterized experimentally. To this end, we have
investigated the folding mechanisms of two homologous threestate
proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the
early and late transition states on their folding pathways. Through
a combination of value analysis and molecular dynamics simulations
we obtained atomic-level structures of the transition states
of these homologous three-state proteins and found that the late
transition states are much more structurally similar than the early
ones. Our findings thus reveal that, while the native state topology
defines essentially in a unique way the late stages of folding, it
leaves significant freedom to the early events, a result that reflects
the funneling of the free energy landscape toward the native state.
