Linked Life Data

19703931

Source:http://linkedlifedata.com/resource/pubmed/id/19703931

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-12-1
pubmed:abstractText
The glycosylphosphatidylinositol (GPI)-anchored prion protein (PrP(C)), usually associated with neurodegenerative diseases, modulates various cellular responses and may scaffold multiprotein cell surface signaling complexes. Engagement of PrP(C) with the secretable cochaperone hop/STI1 induces neurotrophic transmembrane signals through unknown molecular mechanisms. We addressed whether interaction of PrP(C) and hop/STI1 entails structural rearrangements relevant for signaling. Using recombinant wild-type and mutant mouse proteins and binding peptides, we measured circular dichroism (CD), fluorescence spectroscopy, and small angle X-ray scattering (SAXS). PrP(C):hop/STI1 interaction triggers loss of PrP helical structures, involving at least a perturbation of the PrP(143-153) alpha-helix, but no secondary structural modification of hop/STI1 was detected. Novel SAXS models revealed a significant C-terminal compaction of hop/STI1 when bound to PrP. Differing from a recent dimeric model of human hop/STI1, both size-exclusion chromatography and SAXS data support a monomeric form of free murine hop/STI1. Changes in the PrP(143-153) alpha-helix may engage the transmembrane signaling proteins laminin receptor precursor and neural cell adhesion molecule, both of which bind that domain of PrP(C), and further ligands may be engaged by the tertiary structural changes of hop/STI1. These reciprocal structural modifications indicate a versatile mechanism for signaling mediated by PrP(C):hop/STI1 interaction, consistent with the hypothesis of PrP(C)-dependent multiprotein signaling complexes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4308-16
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Reciprocal remodeling upon binding of the prion protein to its signaling partner hop/STI1.
pubmed:affiliation
Instituto de Biofísica da UFRJ, CCS, Bloco G, Cidade Universitária, RJ 21941-902, Brazil.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't