KEY PUBLICATIONS

Bacterial coexistence driven by motility and spatial competition
Sebastian Gude et al. | Nature 578, 588-592 (2020) | pdf & DOI
Processive extrusion of polypeptide loops by a Hsp100 disaggregase
Mario Avellaneda et al. | Nature 578, 317-320 (2020) | pdf & DOI
Alternative modes of client binding enable functional plasticity of Hsp70
Alireza Mashaghi et al. | Nature 539, 448-451 (2016) | pdf & DOI: 10.1038/nature20137
Stochasticity of metabolism and growth at the single-cell level
Daniel J. Kiviet et al. | Nature 514, 376-379 (2014) | pdf & DOI: 10.1038/nature13582
Reshaping of the conformational search of a protein by the chaperone trigger factor
Alireza Mashaghi et al. | Nature 500, 98-101 (2013) | pdf & DOI: 10.1038/nature12293
Tradeoffs and optimality in the evolution of gene regulation
Frank J. Poelwijk et al. | Cell 146, 462-470 (2011) | pdf & DOI:10.1016/j.cell.2011.06.035
Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway
Philipp Bechtluft, Ruud van Leeuwen et al. | Science 318:1458-1461 (2007) | pdf & DOI:10.1126/science.1144972
Empirical fitness landscapes reveal accessible evolutionary paths
Frank Poelwijk, Daan Kiviet et al. | Nature 445:383-386 (2007) | pdf & DOI:10.1038/nature05451
The bacteriophage phi29 portal motor can package DNA against a large internal force
Douglas E. Smith, Sander J. Tans et al. | Nature 413:748-52 (2001) | pdf & DOI:10.1038/35099581
Molecular transistors: Potential modulations along carbon nanotubes
Sander J. Tans, Cees Dekker. | Nature 404:834-35 (2000) | pdf & DOI:10.1038/35009026
Imaging electron wave functions of quantized energy levels in carbon nanotubes
Liesbeth C. Venema et al. | Science 283:52-55 (1999) | pdf & DOI:10.1126/science.283.5398.52
Electron-electron correlations in carbon nanotubes
Sander J. Tans et al. | Nature 394:761-64 (1998) | pdf & DOI:10.1038/29494
Room-temperature transistor based on a single carbon nanotube
Sander J. Tans, Alwin R. M. Verschueren & Cees Dekker | Nature 393:49-52 (1998) | pdf & DOI:10.1038/29954
Individual single-wall carbon nanotubes as quantum wires
Sander J. Tans et al. | Nature 386:474-77 (1997) | pdf & DOI:10.1038/386474a0
Fullerene 'crop circles'
Jie Liu et al. | Nature 385, 780-781 (1997) | pdf & DOI:10.1038/385780b0

The Trigger Factor Chaperone Encapsulates and Stabilizes Partial Folds of Substrate Proteins

Singhal, K.; Vreede, J.; Mashaghi, A.; Tans, S. J.; Bolhuis, P. G.
Abstract:
How chaperones interact with protein chains to assist in their folding is a central open question in biology. Obtaining atomistic insight is challenging in particular, given the transient nature of the chaperone-substrate complexes and the large system sizes. Recent single-molecule experiments have shown that the chaperone Trigger Factor (TF) not only binds unfolded protein chains, but can also guide protein chains to their native state by interacting with partially folded structures. Here, we used all-atom MD simulations to provide atomistic insights into how Trigger Factor achieves this chaperone function. Our results indicate a crucial role for the tips of the finger-like appendages of TF in the early interactions with both unfolded chains and partially folded structures. Unfolded chains are kinetically trapped when bound to TF, which suppresses the formation of transient, non-native end-to-end contacts. Mechanical flexibility allows TF to hold partially folded structures with two tips (in a pinching configuration), and to stabilize them by wrapping around its appendages. This encapsulation mechanism is distinct from that of chaperones such as GroEL, and allows folded structures of diverse size and composition to be protected from aggregation and misfolding interactions. The results suggest that an ATP cycle is not required to enable both encapsulation and liberation.
Year:
2015
Type of Publication:
Article
Journal:
PLoS Comput. Biol.
Volume:
11
Number:
10
Pages:
e1004444
Month:
October
Note:
[PubMed Central:\href{https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626277}{PMC4626277}] [DOI:\href{https://dx.doi.org/10.1371/journal.pcbi.1004444}{10.1371/journal.pcbi.1004444}] [PubMed:\href{https://www.ncbi.nlm.nih.gov/pubmed/26512985}{26512985}]
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