Abstract
The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed aSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.
| Original language | English |
|---|---|
| Pages (from-to) | 55-65 |
| Number of pages | 11 |
| Journal | Journal of Biochemistry |
| Volume | 161 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2017 Jan 1 |
Fingerprint
Keywords
- Amyloid fibril
- GroES
- Toxic intermediate
- XFEL-CXDI
- α-synuclein
ASJC Scopus subject areas
- Medicine(all)
- Biochemistry
- Molecular Biology
Cite this
Common structural features of toxic intermediates from α-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging. / Kameda, Hiroshi; Usugi, Sayaka; Kobayashi, Mana; Fukui, Naoya; Lee, Seki; Hongo, Kunihiro; Mizobata, Tomohiro; Sekiguchi, Yuki; Masaki, Yu; Kobayashi, Amane; Oroguchi, Tomotaka; Nakasako, Masayoshi; Takayama, Yuki; Yamamoto, Masaki; Kawata, Yasushi.
In: Journal of Biochemistry, Vol. 161, No. 1, 01.01.2017, p. 55-65.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common structural features of toxic intermediates from α-synuclein and GroES fibrillogenesis detected using cryogenic coherent X-ray diffraction imaging
AU - Kameda, Hiroshi
AU - Usugi, Sayaka
AU - Kobayashi, Mana
AU - Fukui, Naoya
AU - Lee, Seki
AU - Hongo, Kunihiro
AU - Mizobata, Tomohiro
AU - Sekiguchi, Yuki
AU - Masaki, Yu
AU - Kobayashi, Amane
AU - Oroguchi, Tomotaka
AU - Nakasako, Masayoshi
AU - Takayama, Yuki
AU - Yamamoto, Masaki
AU - Kawata, Yasushi
PY - 2017/1/1
Y1 - 2017/1/1
N2 - The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed aSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.
AB - The aggregation and deposition of α-synuclein (αSyn) in neuronal cells is correlated to pathogenesis of Parkinson's disease. Although the mechanism of αSyn aggregation and fibril formation has been studied extensively, the structural hallmarks that are directly responsible for toxicity toward cells are still under debate. Here, we have compared the structural characteristics of the toxic intermediate molecular species of αSyn and similar toxic species of another protein, GroES, using coherent X-ray diffraction analysis. Using coherent X-ray free electron laser pulses of SACLA, we analysed aSyn and GroES fibril intermediate species and characterized various aggregate structures. Unlike previous studies where an annular oligomeric form of αSyn was identified, particle reconstruction from scattering traces suggested that the specific forms of the toxic particles were varied, with the sizes of the particles falling within a specific range. We did however discover a common structural feature in both αSyn and GroES samples; the edges of the detected particles were nearly parallel and produced a characteristic diffraction pattern in the diffraction experiments. The presence of parallel-edged particles in toxic intermediates of αSyn and GroES fibrillogenesis pointed towards a plausible common molecular interface that leads to the formation of mature fibrils.
KW - Amyloid fibril
KW - GroES
KW - Toxic intermediate
KW - XFEL-CXDI
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85014546024&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014546024&partnerID=8YFLogxK
U2 - 10.1093/jb/mvw052
DO - 10.1093/jb/mvw052
M3 - Article
C2 - 27539923
AN - SCOPUS:85014546024
VL - 161
SP - 55
EP - 65
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 1
ER -