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-Structure paper
| タイトル | Structural organization of p62 filaments and the cellular ultrastructure of calcium-rich p62-enwrapped lipid droplet cargo. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 10810, Year 2025 |
| 掲載日 | 2025年11月28日 |
著者 | Sabrina Berkamp / Lisa Jungbluth / Alexandros Katranidis / Siavash Mostafavi / Olivera Korculanin / Peng-Han Lu / Lotte Ickert / Maya M Dierig / Lokesh Sharma / Lipi Thukral / Pitter F Huesgen / Natalia L Kononenko / Jörg Fitter / Rafal E Dunin-Borkowski / Carsten Sachse / ![]() |
| PubMed 要旨 | The selective autophagy receptor p62/SQSTM1 is known to form higher-order filaments in vitro and to undergo liquid-liquid phase separation when mixed with poly-ubiquitin. Here, we determine the full- ...The selective autophagy receptor p62/SQSTM1 is known to form higher-order filaments in vitro and to undergo liquid-liquid phase separation when mixed with poly-ubiquitin. Here, we determine the full-length cryo-EM structure of p62 and elucidate a structured double helical filament scaffold composed of the PB1-domain associated with the flexible C-terminal part and the solvent-accessible major groove. At different pH values and upon binding to soluble LC3, LC3-conjugated membranes and poly-ubiquitin, we observe p62 filament re-arrangements in the form of structural unwinding, disassembly, lateral association and bundling, respectively. In the cellular environment, under conditions of ATG5 knockdown leading to stalled autophagy, we imaged high-contrast layers consisting of p62 oligomers enwrapping lipid droplets by cryogenic electron tomography in situ, which we identified as calcium as well as phosphorus by compositional spectroscopy analysis. Together, we visualize the cellular ultrastructure of p62 oligomers with high calcium content as a potential early stage of autophagy. |
リンク | Nat Commun / PubMed:41315362 / PubMed Central |
| 手法 | EM (らせん対称) |
| 解像度 | 4.5 Å |
| 構造データ | EMDB-52134: double helical p62/SQSTM1 filament |
| 由来 |
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キーワード | PROTEIN FIBRIL / autophagy / filaments / helical reconstruction |
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