Abstract:
: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 three-state proteins, PTP-BL PDZ2 and PSD-95 PDZ3, and compared the early and late transition states on their folding pathways. Through a combination of Phi 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Calosci N,Chi CN,Richter B,Camilloni C,Engström A,Eklund L,Travaglini-Allocatelli C,Gianni S,Vendruscolo M,Jemth Pdoi
10.1073/pnas.0804774105subject
Has Abstractpub_date
2008-12-09 00:00:00pages
19241-6issue
49eissn
0027-8424issn
1091-6490pii
0804774105journal_volume
105pub_type
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