Fig. 1
From: Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1 autophagy adapter
Structure of the ZZ-domain of p62. a Domain architecture of p62. The PB1 domain is responsible for oligomerization and localization. The ZZ-domain recognizes both type-1 and type-2 N-degrons. The TB domain, LIR motif and UBA are involved in the interaction with TRAF6, LC3-family proteins and ubiquitin, respectively. b Transparent molecular surface showing the electrostatic potential of the ZZ-domain. Negatively and positively charged surfaces are colored red and blue, respectively. Side chains of residues that participate in zinc coordination are shown as stick models and bound zinc ions are shown as slate-colored spheres. The built model of the ZZ-domain comprises residues from Val126 to Pro169 and are marked with dots and labeled. c Schematic diagram showing zinc-coordination. The first zinc atom (Zn1) is coordinated by four cysteine residues, and the second zinc (Zn2) by two cysteine and two histidine residues. d Sequence alignment of ZZ-domain structures in the Protein Data Bank (2e5r: human α-dystrobrevin; 2fc7: human ZZZ3 protein; 2dip: human SWIM domain containing protein 2; 4xi6: human mind bomb 1; 1tot: mouse CREB-binding protein). Zinc-coordinated residues are strictly conserved among all ZZ-domains, although key residues involved in the recognition of N-degrons (marked with black arrow-heads) are not conserved. e Ribbon diagram with transparent electrostatic surface showing the structure of the ZZ-domain in complex with R-BiP substrate (REEED). Residues coordinating zinc atoms and key residues in p62 involved in the recognition of N-degrons are shown as stick models with carbon, nitrogen, and oxygen atoms in green, blue and red, respectively. The bound N-degron is also shown as a stick model with carbon atoms in cyan. Residues of the ZZ-domain are labeled black and those of R-BiP are labeled red with the * and subscript “b” next to the sequence number for clarity. f Close-up view of interaction region between the ZZ-domain and R-BiP. Hydrogen bonds are shown as dotted lines and the distance is indicated. g Superposition of the structure of apo-ZZ-domain (gray) with that of the R-BiP complex (green). The two structures are almost identical except for Asn132 indicated by a dotted circle. h Close-up view of conformational change of Asn132 of the ZZ-domain of p62 upon complex formation
