Structural Biology
- A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler
Biochemical data suggest that the SAM-key domain of the budding yeast remodeler Fun30 is required for its nucleosome remodeling activity by regulating the catalytic ATPase.
- The C-terminal tail of CSNAP attenuates the CSN complex
The study demonstrates inhibition of the COP9 signalosome (CSN) complex by a peptide derived from CSNAP, the smallest CSN subunit. The peptide displaces the endogenous CSNAP subunit from the complex, leading to a CSNAP null phenotype that attenuates CSN activity.
- Structural insights into CED-3 activation
They report cryo-EM structures of CED-4 and three CED-4/CED-3 complexes with multiple oligomeric states. CARD–CARD interaction between CED-4 and CED-3 is essential for CED-3 activation and the newly reported dynamic organization of CED-4 regulates the onset of apoptosis.
- Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes
SARS-CoV-1 spike protein is stabilized with engineered disulfide bonds, and cryo-EM imaging of these stabilized S-trimers reveals rare spike conformations.
- Distant sequence regions of JBP1 contribute to J-DNA binding
Structural modeling and mutagenesis reveal that the N-terminus and DNA-binding domain of JBP1 recognize base-J, enabling replication of this epigenetic marker by JBP1’s thymidine hydroxylase domain.
- Structural insights into ubiquitin chain cleavage by Legionella ovarian tumor deubiquitinases
Legionella possesses OTU deubiquitinases (Lot DUBs), which hinder the host ubiquitin system. We performed structural and biochemical analyses on the Lot DUBs and explained how Lot DUBs are different from other OTU-DUBs.
- Crystal structures of dimeric and heptameric mtHsp60 reveal the mechanism of chaperonin inactivation
The crystal structure of the dimeric mtHsp60 from grouper fish has been determined, revealing a symmetrical subunit interaction with an exchanged α-helix connecting the two subunits. This structure provides new insights into the conformational changes of this important chaperonin
- Interaction hub critical for telomerase recruitment and primer-template handling for catalysis
By deleting, mutating, and adding back parts of the telomerase enzyme that extends chromosome ends, we uncover features important for its proper functioning in the cell.
- Characterisation of the OTU domain deubiquitinase complement of Toxoplasma gondii
The OTU deubiquitinase family is expanded in Toxoplasma parasites, and members show preferences for Lys6-, Lys11-, Lys48-, and Lys63-linked ubiquitin chains, and additional specificity for NEDD8. AlphaFold-guided structural analysis reveals cryptic ubiquitin-binding domains with functional importance.
- Structure-based design and characterization of Parkin-activating mutations
Parkin, an E3 ubiquitin ligase involved in Parkinson’s disease, is inactive in the basal state and is activated by PINK1 to mediate mitophagy. Here, we characterized 31 mutations and discovered three that activate Parkin and rescue loss of PINK1 phosphorylation.