Structural Biology
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancersWRN is a key drug target for cancers with microsatellite instability. A crystal structure of the helicase domain of WRN identifies its unique features and provides a basis for structure-guided design of inhibitors.
A double role of the Gal80 N terminus in activation of transcription by Gal4pActivation of gene expression by Gal4p in K. lactis requires an element in the N terminus of KlGal80p that mediates nuclear co-import of KlGal1p and galactokinase inhibition to support the co-inducer function of KlGal1p.
Mps2 links Csm4 and Mps3 to form a telomere-associated LINC complex in budding yeastThe canonical LINC complex is composed of two different transmembrane proteins; this work reveals the heterotrimeric composition of the telomere-associated LINC complex in budding yeast.
Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-FCrystal and single-particle cryo-EM structures reveal how the tetraspanin CD9 interacts with its prototypical partner EWI-F and provide a new concatenation model for the assembly of tetraspanin-enriched microdomains.
Stoichiometry of Rtt109 complexes with Vps75 and histones H3-H4The work determines the relative and absolute stoichiometry of a 5-chain protein complex involved in histone chaperoning and acetylation. Using sedimentation velocity and light scattering, it uncovers a dynamic equilibrium of complex self-association.
CryoEM structure of Drosophila flight muscle thick filaments at 7 Å resolutionRelaxed thick filaments from Drosophila flight muscle show disordered myosin heads, a ribbon arrangement of myosin tails and a novel protein, stretchin-klp, on the filament surface.
Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesisA cryo-EM structure of human Dispatched-1 reveals a unique open conformation of its extracellular domains for Hedgehog ligand binding.
Structure of avian influenza hemagglutinin in complex with a small molecule entry inhibitorThe binding properties of fusion inhibitor CBS1117 to hemagglutinin by x-ray crystallography, NMR, and mutagenesis give insights into mechanism and guidance for chemical optimization.
Structural basis of HapEP88L-linked antifungal triazole resistance in Aspergillus fumigatusThe mutation P88L in subunit HapE of the CCAAT transcription factor causes resistance of Aspergillus fumigatus to azole drugs due to altered binding, bending, and transcription of target promoters.
STAG1 vulnerabilities for exploiting cohesin synthetic lethality in STAG2-deficient cancersThis work highlights the degradation of STAG1 and inhibition of its interaction with cohesin as promising therapeutic strategies for exploiting synthetic lethality to treat STAG2-mutated tumors and lays the groundwork for the discovery of STAG1-directed small molecules.