@article{Tetramerization:1800,
      recid = {1800},
      author = {Song, Kevin Changhun},
      title = {Folding and Misfolding of the Potassium Channel Pore  Domain during Assembly and Tetramerization},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2019-06},
      pages = {99},
      abstract = {This thesis connects the dynamics of Kv1.2 and KcsA  potassium channel pore domain monomers to the kinetics of  tetramerization. In simulations, monomers adopt multiple  conformations with the three helices folded. NMR studies  also find the monomers to be dynamic and structurally  heterogeneous. However, a KcsA construct with a disulfide  bridge engineered between the two transmembrane helices has  an NMR spectrum with well-dispersed peaks, suggesting that  the monomer can be locked into a native-like conformation.  During tetramerization, FRET results indicate that monomers  rapidly oligomerize upon insertion into liposomes, forming  a dense protein-rich phase. Folding within this  protein-rich phase occurs along separate fast and slow  routes, with $\tau_{f}$ $\sim$ 40 and 1500 seconds,  respectively. In contrast, constructs bearing the disulfide  bond mainly fold via the faster pathway, suggesting that  maintaining the TM helices in their native orientation  reduces misfolding. Interestingly, folding is concentration  independent in spite of the tetrameric nature of the  channel, indicating that the rate-limiting step is  unimolecular and occurs after monomer association in  protein-rich phase. Finally, despite its name, the addition  of KcsA's C-terminal ``tetramerization" domain does not  improve the kinetics of tetramerization.},
      url = {http://knowledge.uchicago.edu/record/1800},
      doi = {https://doi.org/10.6082/uchicago.1800},
}