TL;DR
It is demonstrated that FXI activation results in a global reorganization of the homodimer, extending beyond the activation loop to include a significant reorientation of the catalytic domain (CD) relative to the apple-domain (AD) platform.
The first cryo-EM structures of FXIa in complex with its substrate, FIX, and activated FIX (FIXaβ) define the full FXIa:FIX interface providing a structural template for understanding the sequential activation of FIX and for developing a new class of selective allosteric antithrombotic agents.
Caspase-9 (C9) is a key initiator of the intrinsic apoptotic pathway and contains an N-terminal caspase activation and recruitment domain (CARD) that mediates homotypic and heterotypic interactions. While previous studies have shown that C9CARD can form filamentous assemblies under specific conditions, its intrinsic st...
Crimean-Congo hemorrhagic fever virus (CCHFV) is a high-priority pathogen with high case-fatality rates, yet approved therapeutics remain unavailable. The CCHFV L segment encodes a ∼450-kDa RNA-dependent RNA polymerase (L protein) orchestrating viral replication, but its structural mechanisms remain elusive. Here, we p...
p97/VCP ATPase uses adenosine triphosphate (ATP) hydrolysis to remodel protein assemblies and unfold substrates across diverse cellular processes, including protein quality control, membrane fusion, and chromatin regulation. Although cryogenic structural studies have provided valuable snapshots of distinct nucleotide s...
Human cytochrome P450 2C9 (CYP2C9) is a hepatic microsomal enzyme involved in the oxidative metabolism of clinically important drugs, but the structural organization of its oligomeric assemblies outside crystallographic packing environments remains poorly understood. Here, we report the cryo-EM structure of human CYP2C...
Microtubule nucleation by γ-tubulin ring complexes (γ-TuRCs) must be spatiotemporally controlled to avoid major cell division errors. γ-TuRCs are activated by the centrosome-specific binding of a highly conserved centrosomin motif 1 (CM1) domain, but how binding is prevented in the cytosol remains unclear. We provide t...
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