FC0092
p62  -  p62

Biological function
p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. p62 forms helical polymers, which serve as a molecular scaffold for nascent autophagosomes.

Domain organization/sequence features
The N-terminal PB1 domain (1-102 AA) mediates homo- and heterotypic interactions, and also forms helical filaments. The C- terminal UBA domain (389-434 AA) binds ubiquitinated proteins. The flexible, disordered linker between UBA and PB1 embeds interaction sites with LC3 autophagic marker (LIR).

Structural evidence
The PB1 domain as well as its extended form with 20 AA residues form a flexible, but ordered head-to-tail assembly. After residue 168 (also referred to as after ZZ domain) the chain is extended and solvent exposed, and the 3D structure could not be determined. Consequently, the UBA domain, as well as

Biochemical evidence
Binding of polyubiquitinated substrates to the UBA domain changes the assembly state and shortens the filaments.

Structure/Mechanism
Ubiquitin may act by disrupting interaction surfaces involving the UBA domain in the helix critical for the helical assembly stability.

Mechanism category
tethering

Significance
Fuzziness of the linker between the UBA ubiquitinated cargo binding domain and the helical filament forming PB1 domains enables transient interactions between the UBA domain and the filament that provides additional stability for the assembly. Therefore perturbing these interactions by UBA-substrate binding can regulate the assembly state of p62.