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

被引:46
作者
Berkamp, Sabrina [1 ,2 ]
Mostafavi, Siavash [1 ,2 ]
Sachse, Carsten [1 ,2 ,3 ]
机构
[1] Forschungszentrum Julich, Ernst Ruska Ctr Microscopy & Spect Electrons ER C, D-52425 Julich, Germany
[2] Forschungszentrum Julich, JuStruct Julich Ctr Struct Biol, Julich, Germany
[3] Heinrich Heine Univ, Dept Biol, Dusseldorf, Germany
关键词
autophagy; biomolecular condensate; interaction hub; p62; SQSTM1; phase separation; posttranslational modification; scaffold protein; signaling; SELECTIVE AUTOPHAGY SUBSTRATE; TRANSCRIPTION FACTOR NRF2; UBA DOMAIN; P62; FORMS; PHOSPHORYLATION; DEGRADATION; ACTIVATION; NBR1; PROTEINS; RECEPTOR;
D O I
10.1111/febs.15672
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6927 / 6941
页数:15
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