@article{TEXTUAL,
      recid = {8201},
      author = {Han, Xu and Zhang, Dongliang and Hong, Lu and Yu, Daqi and  Wu, Zhaolong and Yang, Tian and Rust, Michael and Tu, Yuhai  and Ouyang, Qi},
      title = {Determining subunit-subunit interaction from statistics of  cryo-EM images: observation of nearest-neighbor coupling in  a circadian clock protein complex},
      journal = {Nature Communications},
      address = {2023-09-22},
      number = {TEXTUAL},
      abstract = {Biological processes are typically actuated by dynamic  multi-subunit molecular complexes. However, interactions  between subunits, which govern the functions of these  complexes, are hard to measure directly. Here, we develop a  general approach combining cryo-EM imaging technology and  statistical modeling and apply it to study the hexameric  clock protein KaiC in Cyanobacteria. By clustering millions  of KaiC monomer images, we identify two major  conformational states of KaiC monomers. We then classify  the conformational states of (>160,000) KaiC hexamers by  the thirteen distinct spatial arrangements of these two  subunit states in the hexamer ring. We find that  distributions of the thirteen hexamer conformational  patterns for two KaiC phosphorylation mutants can be fitted  quantitatively by an Ising model, which reveals a  significant cooperativity between neighboring subunits with  phosphorylation shifting the probability of subunit  conformation. Our results show that a KaiC hexamer can  respond in a switch-like manner to changes in its  phosphorylation level.},
      url = {http://knowledge.uchicago.edu/record/8201},
}