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 electron microscopy, Dan Southworth's lab captured dynamic conformational states and determined a 3D molecular model of the nitric oxide synthase complex. This enzyme is critical in generating nitric oxide for neuronal signaling, blood pressure regulation and immune defense. The research was awarded the cover image and 'Paper of the Week in the Journal of Biological Chemistry, June 13, 2014.

Recent publications

Teixeira F, Castro H, Cruz T, Tse E, Koldewey P, Southworth DR, Tomás AM, Jakob U. “Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum”. Proc Natl Acad Sci U S A. 2015 Feb 17;112(7)

Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, Southworth DR, Schwappach B, Jakob U. “The protein targeting factor GET3 moonlights as ATP independent chaperone under oxidative stress conditions.” Molecular Cell, 2014 September 16.

Yokom AL, Morishima Y, Lau M, Su M, Glukhova A, Osawa Y, Southworth DR. “Architecture of the Nitric Oxide Synthase Holoenzyme Reveals Large Conformational Changes and a Calmodulin-Driven Release of the FMN Domain.” J Biol Chem. 2014 Apr 19.