Daniel Southworth

Our Research

In the Southworth lab, 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.

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 described the structure of the human Hsp90:Hop complex as it receives proteins from the Hsp70 chaperone. Little is known about the mechanisms of client protein binding, and Hsp90 may be the least understood of the chaperone proteins that facilitate the process. The research was published in Molecular Cell.

Recent publications

Cunningham, C.N., Southworth, DR, Krukenberg, K.A., Agard, D.A. (2012). The conserved arginine 380 of Hsp90 is not a catalytic residue, but stabilizes the closed conformation required for ATP hydrolysis Protein Science, 21 (8), pp. 1162-1171.

Southworth DR and Agard DA. (2011). Client-loading conformation revealed in the cryo-EM structure of the human Hsp90:Hop molecular chaperone complex. Molecular Cell, 2011 Jun 24;42(6): 771-81.