Comparison of successive transition states for folding reveals alternative early folding pathways of two homologous proteins.

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.

authors

Calosci N,Chi CN,Richter B,Camilloni C,Engström A,Eklund L,Travaglini-Allocatelli C,Gianni S,Vendruscolo M,Jemth P

doi

10.1073/pnas.0804774105

subject

Has Abstract

pub_date

2008-12-09 00:00:00

pages

19241-6

issue

49

eissn

0027-8424

issn

1091-6490

pii

0804774105

journal_volume

105

pub_type

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