2000 Fiscal Year Final Research Report Summary
Three-dimensional structure of tandem repeats within RNA polymerase II, prion, and LEA proteins
| Project/Area Number |
10680637
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biophysics
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MATSUSHIMA Norio Sapporo Medical University, School of Health Sciences, Professor, 保健医療学部, 教授 (60137403)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Prion / RNA polymrase II / Tandem repeats / NMR / β-turn |
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| Research Abstract |
The "prion hypothesis" holds that an aberrant conformation of a normal cellular prion protein is the essential, perhaps sole, component of infection agent responsible for several fatal neurodegenerative diseases, including the human genetic disease CJB.The N-terminal region of the prion protein contains five tandem repeats with the consensus sequence of PHGGGWGQ.NMR studies were performed in water for four peptides including C^1R^2Q^3P^4H^5G^6G^7S^8W^9G^<10>Q^<11>R^<12>D^<13>C^<14> (L1). The patterns of the C_αH chemical shift difference of these four peptide mimetics were very similar to those observed for the tandem repeats of human prion protein reported by other researchers. The medium-range NOE connectivities were found between the C_βH of the H5 and the proton of the W9 side chain for L1. These observations indicate that histidine (i) is in close proximity to tryptophan (i+4). Structure calculations for L1 showed that HGG (G/S) W and (G/S) WGQ adopt a loop conformation and a β-turn, respectively.
The carboxyl terminal domain (CTD) of RNA polymerase II, which is rich in phosphorylation sites, contains 17-52 tandem repeats with the consensus sequence of the heptapeptide, YSPTSPS.The repeat unit of the heptapeptide has two SPXX motifs showing potential β-turns, SPTS and SPSY.NMR studies were performed in water at pH4.0 for two cyclic peptides containing one and two repeat units, cyclo-[C^1R^2D^3Y^4S^5P^6T^7S^8P^9S^<10>Y^<11>S^<12>R^<13>D^<14>C^<15>] and cyclo-[C^1R^2D^3Y^4S^5P^6T^7S^8P^9S^<10>Y^<11>S^<12>P^<13>T^<14>S^<15>P^<16>N^<17>Y^<18>S^<19>R^<20>D^<21>C^<22>]. Conformations consistent with NMR parameters including NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers for the SPTS segment. One of the two corresponds to a type I β-turn.
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Research Products
(10 results)
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[Publications] Matsushima,N.,Ohyanagi,T.,Tanaka,T. and Kretsinger,R.H.: "Super-motifs and evolution of super-motifs of tandem leuine-rich repeats within small proteoglycans-biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, epiphycan, and osteoglycin"Proteins;structure,function and genetics. 38(2). 210-225 (2000)
Description
「研究成果報告書概要(和文)」より
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[Publications] Matsushima, N., Ohyanagi, T., Tanaka, T.and Kretsinger, R.H.: "Super-motifs and evolution of super-motifs of tandem leuine-rich repeats within small proteoglycans-biglycan, decorin, lumican, fibromodulin, PRELP, keratocan, epiphycan, and osteoglycin"Proteins ; structure, function and genetics. 38. 210-225 (2000)
Description
「研究成果報告書概要(欧文)」より
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