Daniel Southworth

Our Research

We use cryo-electron microscopy to determine the structure of dynamic protein complexes central to cellular signaling and homeostasis. This structural focus is coupled to key biochemical methods in order to directly attribute biological mechanisms to the protein: protein interactions and conformational changes we identify at the single molecule level. Specifically, we are focused on understanding how molecular chaperones and co-regulatory proteins function at the interface of protein folding, activation and degradation pathways.

Cryo-EM Lab: www.lsi.umich.edu/cryo-em

About Daniel Southworth

  • Cryo-EM
  • Molecular Chaperones
  • Macromolecules

Dan Southworth studies the structure and function of molecular chaperone assemblies central to the protein triage process, the molecular ‘decision’ to degrade or activate substrates. He uses cryo-electron microscopy and in vitro biochemical methods.

Research highlight

Using cryo electron microscopy, Dan Southworth's lab captured dynamic conformational states and determined 3D structures of the conserved RVB1/2 AAA+ complex. This enzyme complex is critical for driving the assembly and activity of diverse macromolecules including chromatin remodelers and ribonucleoprotein complexes. In this work, the Southworth lab determined structures of different nucleotide-bound forms that identify how ATP binding and hydrolysis power this macromolecular machine.

Recent publications

Ewens CA, Su M, Zhao L, Nano N, Houry WA and Southworth DR. “Architecture and Nucleotide-Dependent Conformational Changes of the Rvb1-Rvb2 AAA+ Complex Revealed by Cryo-Electron Microscopy.” Structure. 2016 May 3

Skiniotis G, and Southworth DR. Single-particle cryo-electron microscopy of macromolecular complexes. Review. Microscopy (Oxf). 2015 Nov 25

Rajagopal P, Tse E, Borst AJ, Delbecq SP, Shi L, Dove KK, Baker D, *Southworth DR, and *Klevit RE. “A conserved histidine modulates HSPB5 structure to trigger chaperone activity in response to stress-related acidosis.” Elife. 2015 May 11.