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Cryo-electron microscopy structures of the human AP-1 complex bound to a cargo containing tandem sorting motifs reveal that a single cargo molecule bearing tandem motifs can bridge two neighboring AP-1 complexes through a previously unrecognized μ1-σ1 inter-complex interface, thereby promoting adaptor oligomerization.
In Parkinson's disease (PD), where complex mechanisms and limited targets hamper therapy development, XunZi identifies aberrant activation of CHK2 and IRAK4 kinases across multiple models and establishes a paradigm-shifting framework to translate fragmented biomedical knowledge and data into actionable therapeutics.
An AMBRA1-RMC1-HUWE1 signaling axis that directs HUWE1-mediated ubiquitination to mitochondria to regulate neural development is identified and mitochondrial quality-control enhancement as a potential therapeutic strategy is suggested.
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