1999 Fiscal Year Final Research Report Summary
MOLECULAR MECHANISMS FOR PRION PROTEIN CONVERSION AND CELL-TYPES INVOLVED IN THE CONVERSION IN VIVO
| Project/Area Number |
09470154
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | NAGASAKI UNIVERSITY |
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Principal Investigator |
KATAMINE Shigeru NAGASAKI UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF BACTERIOLOGY, PROFESSOR, 医学部, 教授 (40161062)
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| Co-Investigator(Kenkyū-buntansha) |
SHIGRMATSU Kazuto NAGASAKI UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF PATHOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20154205)
SAKAGUCHI Suehiro NAGASAKI UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF BACTERIOLOGY, ASSISTANT PROFESSOR, 医学部, 講師 (60274635)
SHIRABE Susumu NAGASAKI UNIVERSITY HOSPITAL, FIRST DEPARTMENT OF INTERNAL MEDICINE, LECTURER, 医学部・附属病院, 助手 (40264220)
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| Project Period (FY) |
1997 – 1999
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| Keywords | PRION DISEASES / PRION PROTEIN / PEPTIDES / THERAPEUTICS / PROTEIN-PROTEIN INTERACTION |
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| Research Abstract |
Post-translational conversion of prion protein (PrP) is thought to be the nature of prion propagation. In the present study, we identified aberrant mRNA species in the brain of an ataxic mouse line, Ngsk PrnpィイD10/0ィエD1, lacking PrP. These mRNAs are chimeric between the non-coding exons l/2 of PrP gene (Prnp) and the novel sequence encoding PrP-like protein (PrPLP), a putative membrane glycoprotein with 22% identity with PrP in the primary amino acid structure. Rabbit antiserum raised against recombinant PrPLP specifically immunoprecipitated a protein (m.w.: 19 kD) from lysates of A293T cells transfected with an expression vector. Physical association of PrPLP with PrP was demonstrated in both cell-free system (IAsys cuvette) and transfected cells, suggesting a functional interaction of the two proteins. In addition, by screening a random peptide (12-mer) library, we identified 3 synthetic peptides with a potential of high affinity binding to PrP. Interestingly, one of them reduced the level of the proteinase K-resistant pathogenic form of PrP in vitro with a dose-dependent manner. Both PrPLP and the PrP-binding peptides would be valuable reagents to elucidate molecular mechanisms for the PrP conversion and allow for the development of therapeutics of prion diseases.
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