p62/SQSTM1 can be considered one of the archetypical autophagy receptors, which is centrally involved in the recognition and subsequent disposal of ubiquitinated cargo through autophagy. Moreover, p62 is also known to act in a wide range of signaling activities affecting nutrient sensing, oxidative stress, infection, immunity and inflammation. We have shown that p62 forms flexible filamentous structures by an N-terminal PB1 domain-scaffold that hosts a C-terminal binding platform with critical interaction motifs (Ciuffa et al. 2015). In the cellular environment, p62 filaments have been localized in so-called p62 bodies (Jakobi et al., 2020) that were shown to display properties of liquid-liquid phase separation. We study the structural biology of these filamentous biomolecular condensates and will further shed light on their structural and functional interaction partners in the cell (recently reviewed in Berkamp, Mostafavi et al. 2020).
- Ciuffa, R., Lamark, T., Tarafder, A.K., Guesdon, A., Rybina, S., Hagen, W.J.H., Johansen, T., and Sachse, C. The Selective Autophagy Receptor p62 Forms a Flexible Filamentous Helical Scaffold. (2015) Cell Rep 11, 748–758.
- Jakobi A.J., Huber S.T., Mortensen S.A., Schultz S.W., Palara A., Kuhm T., Shrestha B.K., Lamark T., Hagen W.J.H., Wilmanns M., Johansen T., Brech A., and Sachse C. (2020) Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake. Nat Commun 11(1):440.
- Berkamp S., Mostafavi S., and Sachse C. (2020) Structure and Function of p62/SQSTM1 in the emerging framework of phase separation. FEBS Letters doi: 10.1111/febs.15672.