Conformational stability of the RNP domain controls fibril formation of PABPN1.

ABSTRACT: The disease oculopharyngeal muscular dystrophy is caused by alanine codon trinucleotide expansions in the N-terminal segment of the nuclear poly(A) binding protein PABPN1. As histochemical features of the disease, intranuclear inclusions of PABPN1 have been reported. Whereas the purified N-terminal domain of PABPN1 forms fibrils in an alanine-dependent way, fibril formation of the full-length protein occurs also in the absence of alanines. Here, we addressed the question whether the stability of the RNP domain or domain swapping within the RNP domain may add to fibril formation. A variant of full-length PABPN1 with a stabilizing disulfide bond at position 185/201 in the RNP domain fibrillized in a redox-sensitive manner suggesting that the integrity of the RNP domain may contribute to fibr

SUBMITTER: Liebold J 

PROVIDER: S-EPMC4622212 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature