6TGP

Cryo-EM structure of AtNBR1-PB1 filament (S-type)

Summary for 6TGP

• Entry DOI: 10.2210/pdb6tgp/pdb
• EMDB information: 10500
• Descriptor: Protein NBR1 homolog (1 entity in total)
• Functional Keywords: autophagy, helical filament, signaling protein
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 2
• Total formula weight: 20397.11

Authors

Jakobi, A.J.,Sachse, C. (deposition date: 2019-11-17, release date: 2020-02-19, Last modification date: 2024-05-22)

Primary citation

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.,Sachse, C.
Structural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake.
Nat Commun, 11:440-440, 2020

PubMed Abstract: p62/SQSTM1 is an autophagy receptor and signaling adaptor with an N-terminal PB1 domain that forms the scaffold of phase-separated p62 bodies in the cell. The molecular determinants that govern PB1 domain filament formation in vitro remain to be determined and the role of p62 filaments inside the cell is currently unclear. We here determine four high-resolution cryo-EM structures of different human and Arabidopsis PB1 domain assemblies and observed a filamentous ultrastructure of p62/SQSTM1 bodies using correlative cellular EM. We show that oligomerization or polymerization, driven by a double arginine finger in the PB1 domain, is a general requirement for lysosomal targeting of p62. Furthermore, the filamentous assembly state of p62 is required for autophagosomal processing of the p62-specific cargo KEAP1. Our results show that using such mechanisms, p62 filaments can be critical for cargo uptake in autophagy and are an integral part of phase-separated p62 bodies.

PubMed: 31974402
DOI: 10.1038/s41467-020-14343-8

Experimental method

ELECTRON MICROSCOPY (4.4 Å)