Aggregation of prion protein with insertion mutations is proportional to the number of inserts.

Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Research Abstract Details 

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Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Abstract Text:

Shuiliang Yu,Shaoman Yin,Chaoyang Li,Poki Wong,Binggong Chang,Fan Xiao,Shin-Chung Kang,Huimin Yan,Gengfu Xiao,Po Tien,Man-Sun Sy,

Mutation in the prion gene, PRNP, accounts for approx. 10-15% of human prion diseases. However, little is known about the mechanisms by which a mutant prion protein (PrP) causes disease. We compared the biochemical properties of a wild-type human prion protein, rPrP(C) (recombinant wild-type PrP), which has five octapeptide-repeats, with two recombinant human prion proteins with insertion mutations, one with three more octapeptide repeats, rPrP(8OR), and the other with five more octapeptide repeats, rPrP(10OR). We found that the insertion mutant proteins are more prone to aggregate, and the degree and kinetics of aggregation are proportional to the number of inserts. The octapeptide-repeat and alpha-helix 1 regions are important in aggregate formation, because aggregation is inhibited with monoclonal antibodies that are specific for epitopes in these regions. We also showed that a small amount of mutant protein could enhance the formation of mixed aggregates that are composed of mutant protein and wild-type rPrP(C). Accordingly, rPrP(10OR) is also more efficient in promoting the aggregation of rPrP(C) than rPrP(8OR). These findings provide a biochemical explanation for the clinical observations that the severity of the disease in patients with insertion mutations is proportional to the number of inserts, and thus have implications for the pathogenesis of inherited human prion disease.

Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Publishing Authors By Initials

S Yu,S Yin,C Li,P Wong,B Chang,F Xiao,SC Kang,H Yan,G Xiao,P Tien,MS Sy,

For similar proteins: recombinant proteins research abstracts see: proteins: recombinant proteins research

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Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Biochemical journal

VOLUME: 403

Page Numbers: 343-51

Journal Abbreviation: Biochem. J.

ISSN: 1470-8728

DAY: 15

MONTH: Apr

YEAR: 2007

Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Information

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LANGUAGE: eng

NlmUniqueID: 2984726

Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Keywords Mesh Terms:

KEYWORDS: Recombinant Proteins

MESH TERMS: metabolism

Chemical & Substance for Abstract: Aggregation of prion protein with insertion mutations is proportional to the number of inserts. Information

Substance Name: Recombinant Proteins

Registry Number: 0

Grant and Affiliation Information for Aggregation of prion protein with insertion mutations is proportional to the number of inserts.

AFFILIATION: Department of Pathology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44120, USA.

Country: England

AGENCY: United States NINDS

GRANT: NS-045981-01

ACRONYM: NS

MEDLINETA: Biochem J

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