The interconversion between a flexible β-sheet and a fibril β-arrangement constitutes the main conformational event during misfolding of PSD95-PDZ3 domain.

ABSTRACT: The temperature-induced misfolding pathway of PDZ3, the third PDZ domain of the PSD95 neuronal protein, is populated by a trimeric β-sheet-rich intermediate state that leads to a stepwise and reversible formation of supramacromolecular structures. Using FTIR, we have found that misfolding of this pathway is not due to different ensembles of a variety of precursors, but comes mainly from the interconversion of a flexible β-sheet of the domain to wormlike fibrils. The appearance of the wormlike fibril FTIR component is also accompanied by a slight decrease of the band that corresponds to loops in the native state, whereas the rest of the regular elements of secondary structure are fairly well maintained upon misfolding. Transmission electron microscope micrographs have confirmed the presence

SUBMITTER: Marin-Argany M 

PROVIDER: S-EPMC3443772 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature