哺乳類におけるULK1、ATG13、FIP200の三者相互作用がULKコンプレックス形成とオートファジーに必要不可欠である
哺乳類のオートファゾーム形成の開始には、ULK1/2、ATG13、ATG101、FIP200からなるULKコンプレックスが重要な役割を果たす。本研究では、AlphaFold2を用いて予測したULK1-ATG13-FIP200の三者相互作用の構造的基盤を実験的に確認し、この三者相互作用がオートファジー活性化に必須であることを明らかにした。
Structural Basis and Mechanism of ULK Complex Formation for Autophagy Initiation in Mammals
The triadic interaction among ULK1, ATG13, and FIP200 is crucial for the formation and function of the ULK complex, which initiates autophagosome formation in mammals.
Phase Transition of WTAP Regulates m6A Modification of Interferon-Stimulated Genes
IFN-β-induced dephosphorylation of WTAP promotes its phase transition from aggregates to liquid droplets, which enables WTAP to recruit the m6A methyltransferase complex and transcription factor STAT1 to the promoter regions of interferon-stimulated genes, leading to co-transcriptional m6A modification and regulation of ISG expression.
Short Heat Shock Factor A2 Confers Extreme Heat Sensitivity in Arabidopsis: Insights into Balancing Heat Resistance and Plant Growth
Short heat shock factors S-HsfA2, S-HsfA4c, and S-HsfB1 represent new types of heat shock factors that bind to a novel heat-regulated element and negatively regulate extreme heat tolerance in Arabidopsis to maintain proper plant growth.
Alanyl-tRNA Synthetases AARS1 and AARS2 Regulate cGAS Activity through Lactylation in Response to L-Lactate
AARS1 and AARS2 act as intracellular l-lactate sensors and lactyltransferases that inactivate cGAS, a key regulator of innate immunity, through lactylation.
Small Molecules Facilitate Protein Relocation to Treat Cellular Mislocalization Disorders
Small molecules can help relocate misplaced proteins by facilitating their interactions with shuttle proteins that transport them between the cytoplasm and nucleus.
Harnessing Protein Transport Coupling to Achieve Targeted Protein Relocalization for Therapeutic Potential
Subcellular protein localization can be modulated through molecular coupling to shuttle proteins, enabling the rewiring of the interactome to address disease-driving phenotypes.
Precise Regulation of Transposon Methylation in Germline Development Requires Two-Factor Authentication in the piRNA Pathway
The piRNA pathway precisely regulates DNA methylation of young, active transposons during germline development in male mice through a two-factor authentication process involving the recruitment of SPIN1-SPOCD1 complex to young LINE1 promoters, followed by engagement of MIWI2 with the nascent transcript.
Mechanism of BRCA1-BARD1 Complex in Regulating DNA End Resection and Protecting DNA Integrity
The BRCA1-BARD1 complex plays a dual role in DNA repair - it directly promotes long-range DNA end resection to initiate homologous recombination, while also protecting DNA from unscheduled degradation during replication stress, with the balance between these functions determined by the presence and concentration of the recombinase RAD51.
Structure and Functional Insights into the Human TIP60-C Chromatin Remodeling Complex
The human TIP60-C complex is a 20-subunit chromatin remodeling assembly that integrates histone exchange and acetylation activities, providing insights into the structural organization and recruitment mechanisms of this key regulator of chromatin dynamics.
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