Structural basis of the day-night transition in a bacterial circadian clock

Tseng, Roger; Goularte, Nicolette F.; Chavan, Archana G.; Luu, Jansen; Cohen, Susan E.; Chang, Yong‐Gang; Heisler, Joel; Li, Sheng; Michael, Alicia K.; Tripathi, Sarvind; Golden, Susan S.; LiWang, Andy; Partch, Carrie L.

doi:10.1126/science.aag2516

Cited by 161 publications

(268 citation statements)

References 81 publications

(140 reference statements)

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“…In contrast to the original conformational-selection scheme proposed in Chang's experiment 21 , the present scheme works even when the conformational transition of KaiB is arbitrarily fast, which is thus also consistent with the conclusion of Mukaiyama's experiment 22 . The key points of the present scheme are three-fold: the low concentration of KaiB 21 , the hexameric form of KaiC, and the attractive adjacent KaiB-KaiB interaction in the KaiB-KaiC complex 17,24 . In the next section, we show that the slowness of the binding in Chang's experiment 21 may arise from the low concentration of KaiB.…”

Section: /15mentioning

confidence: 99%

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An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

Koda

Saito

2020

Preprint

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The biological clock of cyanobacteria is composed of three proteins, KaiA, KaiB, and KaiC. The KaiB-KaiC binding brings the slowness into the system, which is essential for the long period of the circadian rhythm.However, there is no consensus as to the origin of the slowness due to the pre-binding conformational transition of either KaiB or KaiC. In this study, we propose a simple KaiB-KaiC binding scheme in a hexameric form with an attractive interaction between adjacent bound KaiB monomers, which is independent of KaiB's conformational change. We then show that the present scheme can explain several important experimental results on the binding, including that used as evidence for the slow conformational transition of KaiB. The present result thus indicates that the slowness arises from KaiC rather than KaiB.

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Section: /15mentioning

confidence: 99%

“…KaiB, on the other hand, inhibits KaiA activity 13,14 , which results in the dephosphorylation of C2. Specifically, after adequate phosphorylation of C2, KaiB binds to C1 and strongly sequesters KaiA from C2 by forming the C1-KaiB-KaiA complex 15 , which has recently been observed directly 16,17 .…”

Section: Introductionmentioning

confidence: 96%

An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

Koda

Saito

2020

Preprint

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“…KaiB, we used six copies of the recent NMR structure (PDB ID: 5JYT) 44 , which shows a foldswitch at the interacting region compared to the previously-determined crystal structure 45 .…”

Section: Kaic-kaib Coarse-grained Integrative Modelling With Haddockmentioning

confidence: 99%

Less is more: Coarse-grained integrative modeling of large biomolecular assemblies with HADDOCK

Roel‐Touris¹,

Don²,

Honorato³

et al. 2019

Preprint

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Predicting the 3D structure of protein interactions remains a challenge in the field of computational structural biology. This is in part due to difficulties in sampling the complex energy landscape of multiple interacting flexible polypeptide chains. Coarse-graining approaches, which reduce the number of degrees of freedom of the system, help address this limitation by smoothing the energy landscape, allowing an easier identification of the global energy minimum. They also accelerate the calculations, allowing to model larger assemblies. Here, we present the implementation of the MARTINI coarse-grained force field for proteins into HADDOCK, our integrative modelling platform. Docking and refinement are performed at the coarse-grained level and the resulting models are then converted back to atomistic resolution through a distance restraints-guided morphing procedure. Our protocol, tested on the largest complexes of the protein docking benchmark 5, shows an overall ~7-fold speed increase compared to standard all-atom calculations, while maintaining a similar accuracy and yielding substantially more near-native solutions. To showcase the potential of our method, we performed simultaneous 7 body docking to model the 1:6 KaiC-KaiB complex, integrating mutagenesis and hydrogen/deuterium exchange data from mass spectrometry with symmetry restraints, and validated the resulting models against a recently published cryo-EM structure.between the number of estimated protein-protein interactions and those deposited in the Protein Data Bank 4 can be overcome based solely on experimental methods 5 .Computational docking has come of age as a complement to experimental methods in order to generate 3D models of protein assemblies. In particular, data-or information-driven docking and other integrative approaches are particularly appealing 1,6-8 . While docking performs sufficiently well for small-and medium-sized proteins, applications to large biological systems, either containing large individual molecules or a large number of interactors, are limited by the significant computational cost of thoroughly sampling complex conformational landscapes.Coarse-grained (CG) models mitigate this limitation by grouping atoms into larger "pseudoatoms" or beads 9-11 , thus reducing the number of particles to consider in the computations. These models were used in the very first energy minimization of a protein in 1969 12 and again in the first docking simulation 13 .Since then, several CG models have been developed and applied to study different aspects of protein structural biology 14 . For protein docking in particular, of the CG models developed over the years, three standouts for their performance and/or success in community assessment experiments: Those implemented in ATTRACT, CABS-dock, and RosettaDock. The ATTRACT model 15,16 , developed by Zacharias and coworkers for flexible protein docking, represents the protein backbone by two pseudo-atoms and the side chains by an additional particle (or two in the case of larger amino acids). ...

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“…There are numerous examples of such coupled folding and binding. 21,[73][74][75][76][77][78][79] In some cases, where the disordered protein is on the edge of being a globular fold, the binding affinity is related to its thermodynamic stability, suggesting a conformational selection mechanism analogous to the equilibrium shifts inferred in 29 Salt, temperature 1J8I (monomer) 2JP1 (dimer) Chloride ion channel protein 30 Redox 1K0M (reduced) 1RK4 (oxidized) Mad2 spindle checkpoint protein 31 Ligand binding 1DUJ (inactive) 1S2H (active) T7 RNA polymerase 32,33 Ligand binding 1QLN (initiation) 1MSW (elongation) Viral fusion proteins 34,35 pH 5HMG (pre-fusion) (e.g., influenza virus hemagglutinin) 1HTM (post-fusion) P1 Lysozyme 36 Redox 1XJU (inactive) 1XJT (active) Circadian clock protein KaiB 37,38 Ligand binding 2QKE (inactive) 5JWR (active) RFaH C-terminal domain (CTD) 39,40 Ligand binding 2OUG (full length) 2LCL (CTD) Selecase 41 Concentration 4QHF (active) 4QHH (inactive) Cytolysin A 42 Membrane insertion 1QOY (monomer) 2WCD (protomer) Phytochromes 43,44 Light 4O0P (dark) 4O01 (light) Retinoic acid receptor 45 Ligand binding 1DKF (antagonist) 3KMR (agonist) TCR ectodomain 46 Unknown 2VLM (typical) 3MFF (alternative) Caspase-6 47 Ligand binding 2WDB (free) 3OD5 (bound) XRCC1 48 Redox 1XNT (reduced) 3LQC (oxidized) protein fold switches. This is clearly demonstrated in the complex of subtilisin with its N-terminal prodomain.…”

Section: Disorder-to-order Transitionsmentioning

confidence: 99%

Structural metamorphism and polymorphism in proteins on the brink of thermodynamic stability

Kulkarni

Solomon

et al. 2018

Protein Science

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The classical view of the structure-function paradigm advanced by Anfinsen in the 1960s is that a protein's function is inextricably linked to its three-dimensional structure and is encrypted in its amino acid sequence. However, it is now known that a significant fraction of the proteome consists of intrinsically disordered proteins (IDPs). These proteins populate a polymorphic ensemble of conformations rather than a unique structure but are still capable of performing biological functions. At the boundary, between well-ordered and inherently disordered states are proteins that are on the brink of stability, either weakly stable ordered systems or disordered but on the verge of being stable. In such marginal states, even relatively minor changes can significantly alter the energy landscape, leading to large-scale conformational remodeling. Some proteins on the edge of stability are metamorphic, with the capacity to switch from one fold topology to another in response to an environmental trigger (e.g., pH, temperature/salt, redox). Many IDPs, on the other hand, are marginally unstable such that small perturbations (e.g., phosphorylation, ligands) tip the balance over to a range of ordered, partially ordered, or even more disordered states. In general, the structural transitions described by metamorphic fold switches and polymorphic IDPs possess a number of common features including low or diminished stability, large-scale conformational changes, critical disordered regions, latent or attenuated binding sites, and expansion of function. We suggest that these transitions are, therefore, conceptually and mechanistically analogous, representing adjacent regions in the continuum of order/disorder transitions.

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Structural basis of the day-night transition in a bacterial circadian clock

Cited by 161 publications

References 81 publications

An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

An alternative interpretation of the slow KaiB-KaiC binding of the cyanobacterial clock proteins

Less is more: Coarse-grained integrative modeling of large biomolecular assemblies with HADDOCK

Structural metamorphism and polymorphism in proteins on the brink of thermodynamic stability

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