Linked Life Data

21209075

Source:http://linkedlifedata.com/resource/pubmed/id/21209075

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2011-3-10
pubmed:abstractText
Huntington disease results from an expanded polyglutamine region in the N terminus of the huntingtin protein. HD pathology is characterized by neuronal degeneration and protein inclusions containing N-terminal fragments of mutant huntingtin. Structural information is minimal, though it is believed that mutant huntingtin polyglutamine adopts ? structure upon conversion to a toxic form. To this end, we designed mammalian cell expression constructs encoding compact ? variants of Htt exon 1 N-terminal fragment and tested their ability to aggregate and induce toxicity in cultured neuronal cells. In parallel, we performed molecular dynamics simulations, which indicate that constructs with expanded polyglutamine ?-strands are stabilized by main-chain hydrogen bonding. Finally, we found a correlation between the reactivity to 3B5H10, an expanded polyglutamine antibody that recognizes a compact ? rich hairpin structure, and the ability to induce cell toxicity. These data are consistent with an important role for a compact ? structure in mutant huntingtin-induced cell toxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8188-96
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A compact beta model of huntingtin toxicity.
pubmed:affiliation
Division of Neurobiology, Department of Psychiatry, Children's Medical Surgical Center, Johns Hopkins University School of Medicine, Baltimore, Mayland 21287, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural