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Structure paper

TitleStructural basis of p62/SQSTM1 helical filaments and their role in cellular cargo uptake.
Journal, issue, pagesNat Commun, Vol. 11, Issue 1, Page 440, Year 2020
Publish dateJan 23, 2020
AuthorsArjen J Jakobi / Stefan T Huber / Simon A Mortensen / Sebastian W Schultz / Anthimi Palara / Tanja Kuhm / Birendra Kumar Shrestha / Trond Lamark / Wim J H Hagen / Matthias Wilmanns / Terje Johansen / Andreas Brech / Carsten Sachse /
PubMed Abstractp62/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 ...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.
External linksNat Commun / PubMed:31974402 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution1.53 - 4.4 Å
Structure data

EMDB-10499, PDB-6tgn:
Cryo-EM structure of AtNBR1-PB1 filament (L-type)
Method: EM (helical sym.) / Resolution: 3.9 Å

EMDB-10500, PDB-6tgp:
Cryo-EM structure of AtNBR1-PB1 filament (S-type)
Method: EM (helical sym.) / Resolution: 4.4 Å

EMDB-10501, PDB-6tgy:
Cryo-EM structure of p62-PB1 filament (L-type)
Method: EM (helical sym.) / Resolution: 3.5 Å

EMDB-10502: Cryo-EM structure of p62-PB1 filament (L-type)
PDB-6th3: Cryo-EM structure of p62-PB1 filament (S-type)
Method: EM (helical sym.) / Resolution: 4.0 Å

PDB-6tgs:
AtNBR1-PB1 domain
Method: X-RAY DIFFRACTION / Resolution: 1.53 Å

Chemicals

ChemComp-GOL:
GLYCEROL

ChemComp-PEG:
DI(HYDROXYETHYL)ETHER

ChemComp-SO4:
SULFATE ION

ChemComp-CL:
Unknown entry

ChemComp-SIN:
SUCCINIC ACID

ChemComp-HOH:
WATER

Source
  • arabidopsis thaliana (thale cress)
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / Autophagy / helical filament / APOPTOSIS / CYTOSOLIC PROTEIN

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