Structural Insights into the Ubiquitin-Independent Midnolin-Proteasome Pathway

Academic Background Protein homeostasis (proteostasis) is a core mechanism for maintaining normal cellular function, with the ubiquitin-proteasome system (UPS) responsible for degrading approximately 80% of abnormal proteins. Traditionally, proteins were thought to require ubiquitination for recognition and degradation by the 26S proteasome. Howeve...

Cyclic Peptide Inhibitors Function as Molecular Glues to Stabilize Gq/11 Heterotrimers

Academic Background G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in the human body, transmitting extracellular signals through heterotrimeric G proteins (composed of Gα and Gβγ subunits). G proteins function as molecular switches, with their activity states regulated by the GTP/GDP cycle: - Inactive state: Gα bind...

Cross-Feeding Creates Tipping Points in Microbiome Diversity

Academic Background Microbiomes are among the most diverse ecosystems on Earth, consisting of hundreds of functionally distinct microbial populations interacting through complex resource exchange networks. However, a long-standing unresolved question is: How is this extraordinary diversity maintained through metabolic interactions among populations...

Unconventional Secretion of Park7 Requires Lysosomal Delivery via Chaperone-Mediated Autophagy and Specialized SNARE Complex

1. Research Background The Parkinson’s disease-associated protein PARK7/DJ-1 (hereafter referred to as PARK7) is a multifunctional protein that plays critical roles in various pathological conditions including neurodegenerative diseases, cancer, and inflammation. Despite lacking a conventional N-terminal signal peptide sequence, PARK7 can be secret...

Quantitative Spatial Analysis of Chromatin Biomolecular Condensates Using Cryoelectron Tomography

Academic Background Biomolecular condensates are membrane-less organelles formed through liquid-liquid phase separation (LLPS) within cells, playing critical roles in key biological processes such as gene expression and signal transduction. However, due to limitations in traditional imaging techniques, high-resolution structural information about t...

METTL3 Mediates Atheroprone Flow–Induced Glycolysis in Endothelial Cells

1. Research Background Atherosclerosis is the primary pathological basis of cardiovascular diseases, closely associated with endothelial cell (EC) dysfunction. Hemodynamic factors play a critical role in the regional selectivity of atherosclerosis: oscillatory shear stress (OS) (e.g., at vascular bifurcations) promotes plaque formation, while pulsa...