Imperial College London
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ProfessorKeithWillison

Faculty of Natural Sciences, Department of Chemistry

Chair in Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 5837keith.willison Website CV

 
 
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Location

 

301FMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Willison:2018:10.1042/BCJ20170378,
author = {Willison, KR},
doi = {10.1042/BCJ20170378},
journal = {Biochemical Journal},
pages = {3009--3034},
title = {The structure and evolution of eukaryotic chaperonin containing TCP-1 and its mechanism that folds actin into a protein spring},
url = {http://dx.doi.org/10.1042/BCJ20170378},
volume = {475},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Actin is folded to its native state in eukaryotic cytosol by the sequential allosteric mechanism of the chaperonin-containing TCP-1 (CCT). The CCT machine is a double-ring ATPase built from eight related subunits, CCT1–CCT8. Non-native actin interacts with specific subunits and is annealed slowly through sequential binding and hydrolysis of ATP around and across the ring system. CCT releases a folded but soft ATP-G-actin monomer which is trapped 80kJ/mol uphill on the folding energy surface by its ATP-Mg2+/Ca2+ clasp. The energy landscape can be re-explored in the actin filament, F-actin, because ATP hydrolysis produces dehydrated and more compact ADP-actin monomers which, upon application of force and strain, are opened and closed like the elements of a spring. Actin-based myosin motor systems underpin a multitude of force generation processes in cells and muscles. We propose that the water surface of F-actin acts as a low-binding energy, directional waveguide which is recognized specifically by the myosin lever-arm domain before the system engages to form the tight-binding actomyosin complex. Such a water-mediated recognition process between actin and myosin would enable symmetry breaking through fast, low energy initial binding events. The origin of chaperonins and the subsequent emergence of the CCT–actin system in LECA (last eukaryotic common ancestor) point to the critical role of CCT in facilitating phagocytosis during early eukaryotic evolution and the transition from the bacterial world. The coupling of CCT-folding fluxes to the cell cycle, cell size control networks and cancer are discussed together with directions for further research.
AU  - Willison,KR
DO  - 10.1042/BCJ20170378
EP  - 3034
PY  - 2018///
SN  - 1470-8728
SP  - 3009
TI  - The structure and evolution of eukaryotic chaperonin containing TCP-1 and its mechanism that folds actin into a protein spring
T2  - Biochemical Journal
UR  - http://dx.doi.org/10.1042/BCJ20170378
UR  - http://hdl.handle.net/10044/1/63924
VL  - 475
ER  -
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