title: Single octapeptide deletion selectively processes a pathogenic prion protein mutant on the cell surface.
abstract: The number of octapeptide repeats has been considered to correlate with clinical and pathogenic phenotypes of prion diseases resulting from aberrant metabolism of prion protein (PrP). However, it is still poorly understood how this motif affects PrP metabolism. Here, we discover homozygous single octapeptide repeat deletion mutation in the PRNP gene encoding PrP in HeLa cells. The level of PrP proves to be unaffected by this mutation alone, but selectively reduced by additional pathogenic mutations within internal hydrophobic region of PrP. The pattern and relative amount of newly synthesized A117V mutant is unaffected, whereas the mutant appears to be differentially distributed and processed on the cell surface by single octapeptide deletion. This study provides an insight into a novel mutant-specific metabolism of PrP on the cell surface.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Duri
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Ilho
authors.initials: I
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Youngsup
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine & Asan Institute of Life Sciences, Asan Medical Center, Seoul, Republic of Korea. Electronic address: swkang@amc.seoul.kr.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002462:Cell Membrane / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D011328:Prions / Q000235:genetics*; D011485:Protein Binding; D017384:Sequence Deletion / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D008565:Membrane Proteins; D010455:Peptides; D011328:Prions
keywords: Octapeptide repeats; Prion; Proteostasis; Secretory pathway