Protein aggregation is a hallmark of multiple human pathologies.Autophagy selectively degrades protein aggregates via aggrephagy.How selectivity is achieved has been elusive.Here,we identify the chaperonin subunit CCT2 as an autophagy receptor regulating the clearance of aggregation-prone proteins in the cell and the mouse brain.CCT2 associates with aggregation-prone proteins independent of cargo ubiquitination and interacts with autophagosome marker ATG8s through a non-classical VLIR motif.In addition,CCT2 regulates aggrephagy independently of the ubiquitin-binding receptors(P62,NBR1,and TAX1BP1)or chaperone-mediated autophagy.Unlike P62,NBR1,and TAX1BP1,which facilitate the clearance of protein condensates with liquidity,CCT2 specifically promotes the autophagic degradation of protein aggregates with little liquidity(solid aggregates).Furthermore,aggregation-prone protein accumulation induces the functional switch of CCT2 from a chaperone subunit to an autophagy receptor by promoting CCT2 monomer formation,which exposes the VLIR to ATG8s interaction and,therefore,enables the autophagic function.
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机译:Structure Determination and Mechanistic Insights of: I.Cyanobacteriochrome NpR6012g4 Light Sensor Protein in Phototaxis II.Retinal Degeneration 3 (RD3) Protein in Vision III.Ryanodine Receptor 2 (RyR2) Regulation by Calmodulin (CaM) in Cardiac Function =结构测定和机理洞悉:I.趋光性中的蓝细菌色素NpR6012g4光敏蛋白 II.视觉作用中的视网膜退化蛋白3 III.心脏功能中的钙调蛋白调控兰诺定受体2