Linked Life Data

21182336

Source:http://linkedlifedata.com/resource/pubmed/id/21182336

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-2-1
pubmed:abstractText
To understand how the conformational heterogeneity of protofibrils formed by any protein, as well as the mechanisms of their formation, are modulated by a change in aggregation conditions, we studied the formation of amyloid protofibrils by barstar at low pH by multiple structural probes in the presence of hexafluoroisopropanol (HFIP). In the presence of 10% HFIP, aggregation proceeds with the transient formation of spherical oligomers and leads to the formation of both protofibrils and fibrils. Curly short protofibrils and fibrils are seen to form early during the aggregation reaction, and both are seen to grow gradually in length during the course of the reaction. Atomic force microscopy images reveal that the HFIP-induced protofibrils are long (?300 nm in length), curly, and beaded and appear to be composed primarily of ?-sheet bilayers, with heights of ?2.4 nm. The protofibrils formed in the presence of HFIP differ in both their structures and their stabilities from the protofibrils formed either in the absence of alcohol or in the presence of a related alcohol, trifluoroethanol (TFE). Aggregation appears to proceed via an isodesmic polymerization mechanism. Internal structure in the growing aggregates changes in two stages during protofibril formation. In the first stage, an ?-helix-rich oligomeric intermediate is formed. In the second stage, the level of ?-sheet structure increases at the expense of some ?-helical structure. The second stage itself appears to occur in two distinct steps. The creation of thioflavin T binding sites occurs concomitantly with aggregate elongation and is seen to precede the change in secondary structure. The long straight fibrils with characteristic heights of 8-10 nm, which form in the course of the HFIP-induced aggregation reaction, have not been observed to form either in the absence of alcohol or in the presence of TFE.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
805-19
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Fluoroalcohol-induced modulation of the pathway of amyloid protofibril formation by barstar.
pubmed:affiliation
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't