Yu Y, et al. (2011) Flexibility of the Ure2 prion domain is important for amyloid fibril formation. Biochem J 434(1):143-151
Abstract: Ure2, the protein determinant of the Saccharomyces cerevisiae prion [URE3], has a natively disordered N-terminal domain that is important for prion formation in vivo and amyloid formation in vitro; the globular C-domain has a glutathione transferase-like fold. Here, we swapped the position of the N- and C- regions, with or without an intervening peptide linker, to create the Ure2 variants CLN-Ure2 and CN-Ure2, respectively. The native structural content and stability of the variants were the same as wild-type Ure2, as indicated by enzymatic activity, far-UV circular dichroism and equilibrium denaturation. CLN-Ure2 was able to form amyloid-like fibrils, but with a significantly longer lag time than wild-type Ure2; and the two proteins were unable to cross-seed. Under the same conditions, CN-Ure2 showed limited ability to form fibrils, but this was improved after addition of 0.03 M GdmCl. As for wild-type Ure2, allosteric enzyme activity was observed in fibrils of CLN-Ure2 and CN-Ure2, consistent with retention of native-like dimeric structure of the C-domains within the fibrils. Proteolytically digested fibrils of CLN-Ure2 and CN-Ure2 showed the same residual fibril core morphology as wild-type Ure2. The results suggest that the position of the prion domain affects the ability of Ure2 to form fibrils primarily due to effects on its flexibility.
|Status: Published||Type: Journal Article||PubMed ID: 21091436|
Topics addressed in this paper
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.
|Topics||Genes linked to topics|
|Disease Gene Related|
|Protein Physical Properties|
|Protein Sequence Features|
|Protein/Nucleic Acid Structure|