Structure and function of p62/SQSTM1 in the emerging framework of phase separation

Abstract

p62/SQSTM1 is a multiprotein interaction hub forming cellular punctate structures known as p62 bodies. p62 is centrally involved in the degradation of ubiquitinated cargo through autophagy, as well as in a wide range of signaling activities as part of the cellular response to nutrient sensing, oxidative stress, infection, immunity, and inflammation. Structural work has shown that p62 forms flexible filamentous assemblies composed of an N-terminal PB1-domain scaffold and a C-terminal binding platform, including folded recognition domains and structurally disordered binding motifs. In the cell, these filaments are part of cellular p62 bodies that display properties of liquid-liquid-phase separation. Here, we review the accumulated structural and functional work of p62 and integrate them with the emerging framework of filamentous biomolecular condensates.

Keywords: autophagy; biomolecular condensate; interaction hub; p62/SQSTM1; phase separation; posttranslational modification; scaffold protein; signaling.