Elucidation of Master Allostery Essential for Circadian Clock Oscillation in Cyanobacteria

AbstractSpatio-temporal allostery is the source of complex but ordered biological phenomena. To identify the structural basis for allostery that drives the cyanobacterial circadian clock, we crystallized the clock protein KaiC in four distinct states, which cover a whole cycle of phosphor–transfer events at Ser431 and Thr432. The minimal set of allosteric events required for oscillatory nature is a bidirectional coupling between the coil-to-helix transition of the Ser431-dependent phospho-switch in the C-terminal domain of KaiC and ADP release from its N-terminal domain during ATPase cycle. An engineered KaiC–protein oscillator consisting of a minimal set of the identified master allosteric events exhibited mono-phosphorylation cycle of Ser431 with a temperature-compensated circadian period, providing design principles for simple post-translational biochemical circadian oscillators.One Sentence SummaryCoupling between a phospho-switch and KaiC ATPase-dependent nucleotide exchange drives the cyanobacterial circadian clock.

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Crystal Structure of the Redox-Active Cofactor Dibromothymoquinone Bound to Circadian Clock Protein KaiA and Structural Basis for Dibromothymoquinone’s Ability to Prevent Stimulation of KaiC Phosphorylation by KaiA

Biochemistry ◽

10.1021/bi301222t ◽

2012 ◽

Vol 51 (41) ◽

pp. 8050-8052 ◽

Cited By ~ 8

Author(s):

Rekha Pattanayek ◽

Said K. Sidiqi ◽

Martin Egli

Keyword(s):

Crystal Structure ◽

Circadian Clock ◽

Structural Basis ◽

Redox Active ◽

Clock Protein ◽

Stimulation Of

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Faculty Opinions recommendation of NMR structure of the KaiC-interacting C-terminal domain of KaiA, a circadian clock protein: implications for KaiA-KaiC interaction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1017154.202265 ◽

2004 ◽

Author(s):

Juergen Wiegel

Keyword(s):

Circadian Clock ◽

Nmr Structure ◽

Terminal Domain ◽

Clock Protein

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NMR structure of the KaiC-interacting C-terminal domain of KaiA, a circadian clock protein: Implications for KaiA-KaiC interaction

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0305516101 ◽

2004 ◽

Vol 101 (6) ◽

pp. 1479-1484 ◽

Cited By ~ 49

Author(s):

I. Vakonakis ◽

J. Sun ◽

T. Wu ◽

A. Holzenburg ◽

S. S. Golden ◽

...

Keyword(s):

Circadian Clock ◽

Nmr Structure ◽

Terminal Domain ◽

Clock Protein

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Hexamerization by the N-terminal domain and intersubunit phosphorylation by the C-terminal domain of cyanobacterial circadian clock protein KaiC

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.07.143 ◽

2006 ◽

Vol 348 (3) ◽

pp. 864-872 ◽

Cited By ~ 43

Author(s):

Fumio Hayashi ◽

Ryo Iwase ◽

Tatsuya Uzumaki ◽

Masahiro Ishiura

Keyword(s):

Circadian Clock ◽

Terminal Domain ◽

Clock Protein

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Letter to the Editor: Sequence-specific1H,13C and15N resonance assignments of the C-terminal domain of KaiA, a circadian clock protein

Journal of Biomolecular NMR ◽

10.1023/b:jnmr.0000015373.13794.c7 ◽

2004 ◽

Vol 28 (4) ◽

pp. 403-404 ◽

Cited By ~ 1

Author(s):

Ioannis Vakonakis ◽

Andy C. LiWang

Keyword(s):

Circadian Clock ◽

Resonance Assignments ◽

Terminal Domain ◽

Letter To The Editor ◽

Clock Protein

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Crystal structures of Magnaporthe oryzae trehalose-6-phosphate synthase (MoTps1) suggest a model for catalytic process of Tps1

Biochemical Journal ◽

10.1042/bcj20190289 ◽

2019 ◽

Vol 476 (21) ◽

pp. 3227-3240 ◽

Cited By ~ 1

Author(s):

Shanshan Wang ◽

Yanxiang Zhao ◽

Long Yi ◽

Minghe Shen ◽

Chao Wang ◽

...

Keyword(s):

Crystal Structures ◽

Conformational Changes ◽

Magnaporthe Oryzae ◽

Structural Information ◽

Complex Structure ◽

Critical Role ◽

Catalytic Process ◽

Structural Basis ◽

Salt Bridges ◽

Terminal Domain

Trehalose-6-phosphate (T6P) synthase (Tps1) catalyzes the formation of T6P from UDP-glucose (UDPG) (or GDPG, etc.) and glucose-6-phosphate (G6P), and structural basis of this process has not been well studied. MoTps1 (Magnaporthe oryzae Tps1) plays a critical role in carbon and nitrogen metabolism, but its structural information is unknown. Here we present the crystal structures of MoTps1 apo, binary (with UDPG) and ternary (with UDPG/G6P or UDP/T6P) complexes. MoTps1 consists of two modified Rossmann-fold domains and a catalytic center in-between. Unlike Escherichia coli OtsA (EcOtsA, the Tps1 of E. coli), MoTps1 exists as a mixture of monomer, dimer, and oligomer in solution. Inter-chain salt bridges, which are not fully conserved in EcOtsA, play primary roles in MoTps1 oligomerization. Binding of UDPG by MoTps1 C-terminal domain modifies the substrate pocket of MoTps1. In the MoTps1 ternary complex structure, UDP and T6P, the products of UDPG and G6P, are detected, and substantial conformational rearrangements of N-terminal domain, including structural reshuffling (β3–β4 loop to α0 helix) and movement of a ‘shift region' towards the catalytic centre, are observed. These conformational changes render MoTps1 to a ‘closed' state compared with its ‘open' state in apo or UDPG complex structures. By solving the EcOtsA apo structure, we confirmed that similar ligand binding induced conformational changes also exist in EcOtsA, although no structural reshuffling involved. Based on our research and previous studies, we present a model for the catalytic process of Tps1. Our research provides novel information on MoTps1, Tps1 family, and structure-based antifungal drug design.

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