Determining subunit-subunit interaction from statistics of cryo-EM images: observation of nearest-neighbor coupling in a circadian clock protein complex

Bibliographic Details
Title: Determining subunit-subunit interaction from statistics of cryo-EM images: observation of nearest-neighbor coupling in a circadian clock protein complex
Authors: Xu Han, Dongliang Zhang, Lu Hong, Daqi Yu, Zhaolong Wu, Tian Yang, Michael Rust, Yuhai Tu, Qi Ouyang
Source: Nature Communications, Vol 14, Iss 1, Pp 1-11 (2023)
Publisher Information: Nature Portfolio, 2023.
Publication Year: 2023
Collection: LCC:Science
Subject Terms: Science
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2041-1723
Relation: https://doaj.org/toc/2041-1723
DOI: 10.1038/s41467-023-41575-1
Access URL: https://doaj.org/article/cd37a6687ca9499b982a7ec98d097bb6
Accession Number: edsdoj.37a6687ca9499b982a7ec98d097bb6
Database: Directory of Open Access Journals
More Details
ISSN:20411723
DOI:10.1038/s41467-023-41575-1
Published in:Nature Communications
Language:English