Macromolecular complexes are often composed of diverse subunits. Assembling these monomeric subunits into complexes over time faces fundamental obstacles that can be robustly overcome by exploiting a large design space of kinetic protocols.

Using cryo-EM, the He Laboratory revealed how TFIIIA, TFIIIC, and TFIIIB assemble on the S. cerevisiae 5S rRNA promoter, with TFIIIA bridging TFIIIC-DNA interactions and TFIIIB inducing gene wrapping. smFRET showed DNA bending and partial dissociation, offering insights into Pol III transcription initiation and its distinction from Pol II.

How chromatin-based enzymes find nucleosome-free genomic targets in the cell nucleus has been enigmatic. Using cryo-EM, biochemistry and epigenomics, we found a generalizable mechanism showing that the ATP-driven yeast SWR1 remodeler senses accessible chromatin architecture with a protein module that measures free DNA linked flexibly to histone PTM reader domains, enabling SWR1 capture and histone […]

MCE proteins are major virulence factors in Mycobacterium tuberculosis, the causative agent of tuberculosis, the world’s leading cause of death from a single infectious agent. Here, we describe the endogenous cryo-EM structure of a mycobacterial MCE protein system: a large protein complex of 10+ proteins, this is the first example of a protein complex that […]