Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2006-11-29
pubmed:abstractText
The synucleins are a family of intrinsically disordered proteins involved in various human diseases. alpha-Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while gamma-synuclein is overexpressed in a majority of late-stage breast cancers. Despite fairly strong sequence similarity between the amyloid-forming regions of alpha- and gamma-synuclein, gamma-synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of alpha- and gamma-synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for gamma-synuclein and compared them to previously published shifts for alpha-synuclein. In order to facilitate direct comparison, we have implemented a simple new technique for re-referencing chemical shifts that we have found to be highly effective for both disordered and folded proteins. In addition, we have developed a new method that combines different chemical shifts into a single residue-specific secondary structure propensity (SSP) score. We observe significant differences between alpha- and gamma-synuclein secondary structure propensities. Most interestingly, gamma-synuclein has an increased alpha-helical propensity in the amyloid-forming region that is critical for alpha-synuclein fibrillation, suggesting that increased structural stability in this region may protect against gamma-synuclein aggregation. This comparison of residue-specific secondary structure propensities between intrinsically disordered homologs highlights the sensitivity of transient structure to sequence changes, which we suggest may have been exploited as an evolutionary mechanism for fast modulation of protein structure and, hence, function.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-10639120, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-10781096, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-10828462, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-10908673, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-10978144, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11273710, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11286556, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11371636, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11590151, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11812782, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-11910028, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-12121974, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-12381310, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-12427042, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-12575995, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-12652131, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-14681372, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15024385, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15033366, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15134647, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15231664, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15234983, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15236972, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15365127, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15632170, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15643843, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15737408, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15738986, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-15772753, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16041479, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16140929, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16171820, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16223878, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16269331, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16366524, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16452621, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16551093, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16602695, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16731974, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16773211, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-16780837, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-5061873, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-7664054, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-7731949, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-7830591, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-7984417, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-8520220, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-8743705, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-8876165, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-9094331, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-9254694, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-9809558, http://linkedlifedata.com/resource/pubmed/commentcorrection/17088319-9973226
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0961-8368
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2795-804
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation.
More...