Linked Life Data

14610069

Source:http://linkedlifedata.com/resource/pubmed/id/14610069

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-1-26
pubmed:abstractText
The yeast prion protein Ure2 forms amyloid-like filaments in vivo and in vitro. This ability depends on the N-terminal prion domain, which contains Asn/Gln repeats, a motif thought to cause human disease by forming stable protein aggregates. The Asn/Gln region of the Ure2p prion domain extends to residue 89, but residues 15-42 represent an island of "normal" random sequence, which is highly conserved in related species and is relatively hydrophobic. We compare the time course of structural changes monitored by thioflavin T (ThT) binding fluorescence and atomic force microscopy for Ure2 and a series of prion domain mutants under a range of conditions. Atomic force microscopy height images at successive time points during a single growth experiment showed the sequential appearance of at least four fibril types that could be readily differentiated by height (5, 8, 12, or 9 nm), morphology (twisted or smooth), and/or time of appearance (early or late in the plateau phase of ThT binding). The Ure2 dimer (h = 2.6 +/- 0.5 nm) and granular particles corresponding to higher order oligomers (h = 4-12 nm) could also be detected. The mutants 15Ure2 and Delta 15-42Ure2 showed the same time-dependent variation in fibril types but with an increased lag time detected by ThT binding compared with wild-type Ure2. In addition, Delta 15-42Ure2 showed reduced binding to ThT. The results imply a role of the conserved region in both amyloid nucleation and formation of the binding surface recognized by ThT. Further, Ure2 amyloid formation is a multistep process via a series of fibrillar intermediates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3361-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14610069-Amino Acid Motifs, pubmed-meshheading:14610069-Amino Acid Sequence, pubmed-meshheading:14610069-Amyloid, pubmed-meshheading:14610069-Asparagine, pubmed-meshheading:14610069-Dimerization, pubmed-meshheading:14610069-Glutamine, pubmed-meshheading:14610069-Glutathione Peroxidase, pubmed-meshheading:14610069-Hydrogen-Ion Concentration, pubmed-meshheading:14610069-Kinetics, pubmed-meshheading:14610069-Microscopy, Atomic Force, pubmed-meshheading:14610069-Molecular Sequence Data, pubmed-meshheading:14610069-Mutation, pubmed-meshheading:14610069-Prions, pubmed-meshheading:14610069-Protein Binding, pubmed-meshheading:14610069-Protein Structure, Tertiary, pubmed-meshheading:14610069-Saccharomyces cerevisiae Proteins, pubmed-meshheading:14610069-Sequence Homology, Amino Acid, pubmed-meshheading:14610069-Thiazoles, pubmed-meshheading:14610069-Time Factors
pubmed:year
2004
pubmed:articleTitle
Amyloid nucleation and hierarchical assembly of Ure2p fibrils. Role of asparagine/glutamine repeat and nonrepeat regions of the prion domains.
pubmed:affiliation
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't