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| Title | Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion. |
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| Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3491, Year 2022 |
| Publish date | Jun 17, 2022 |
 Authors | Li-Qiang Wang / Yeyang Ma / Han-Ye Yuan / Kun Zhao / Mu-Ya Zhang / Qiang Wang / Xi Huang / Wen-Chang Xu / Bin Dai / Jie Chen / Dan Li / Delin Zhang / Zhengzhi Wang / Liangyu Zou / Ping Yin / Cong Liu / Yi Liang /  |
| PubMed Abstract | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share ...Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Misfolded Cu, Zn-superoxide dismutase (SOD1) has been linked to both familial and sporadic ALS. SOD1 fibrils formed in vitro share toxic properties with ALS inclusions. Here we produced cytotoxic amyloid fibrils from full-length apo human SOD1 under reducing conditions and determined the atomic structure using cryo-EM. The SOD1 fibril consists of a single protofilament with a left-handed helix. The fibril core exhibits a serpentine fold comprising N-terminal segment (residues 3-55) and C-terminal segment (residues 86-153) with an intrinsic disordered segment. The two segments are zipped up by three salt bridge pairs. By comparison with the structure of apo SOD1 dimer, we propose that eight β-strands (to form a β-barrel) and one α-helix in the subunit of apo SOD1 convert into thirteen β-strands stabilized by five hydrophobic cavities in the SOD1 fibril. Our data provide insights into how SOD1 converts between structurally and functionally distinct states. |
 External links | Nat Commun / PubMed:35715417 / PubMed Central |
| Methods | EM (helical sym.) |
| Resolution | 2.95 Å |
| Structure data | EMDB-32227, PDB-7vzf: |
| Source |
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 Keywords | PROTEIN FIBRIL /  Amyloid fibril |
