Allosteric Transitions in the Chaperonin GroEL are Captured by a Dominant Normal Mode that is Most Robust to Sequence Variations

Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. Allostery describes the responses of a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the structural perturbation method, based on phonon propagation in solids, which can be used to determine the signal-transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Application to the bacterial chaperonin GroEL–GroES complex shows that the AWD determined from structures also drives the allosteric transitions dynamically. From both a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the iterative annealing mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function, in a self-consistent manner. This article is part of a discussion meeting issue ‘Allostery and molecular machines’.

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Allosteric Transitions of Supramolecular Systems Explored by Network Models: Application to Chaperonin GroEL

PLoS Computational Biology ◽

10.1371/journal.pcbi.1000360 ◽

2009 ◽

Vol 5 (4) ◽

pp. e1000360 ◽

Cited By ~ 100

Author(s):

Zheng Yang ◽

Peter Májek ◽

Ivet Bahar

Keyword(s):

Network Models ◽

Supramolecular Systems ◽

Chaperonin Groel ◽

Allosteric Transitions

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Signaling Networks and Dynamics of Allosteric Transitions in Bacterial Chaperonin GroEL: Implications for Iterative Annealing of Misfolded Proteins

10.1101/207431 ◽

2017 ◽

Cited By ~ 1

Author(s):

D. Thirumalai ◽

Changbong Hyeon

Keyword(s):

Signal Transmission ◽

Signaling Networks ◽

Salt Bridges ◽

Wiring Diagram ◽

Chaperonin Groel ◽

Consistent Manner ◽

Allosteric Transitions ◽

Biological Complexes ◽

And Function ◽

Molecular Description

AbstractSignal transmission at the molecular level in many biological complexes occurs through allosteric transitions. They describe the response a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the Structural Perturbation Method (SPM), based on phonon propagation in solids, that can be used to determine the signal transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Applications to the bacterial chaperonin GroEL-GroES complex shows that the AWD determined from structures also drive the allosteric transitions dynamically. Both from a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the Iterative Annealing Mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function in a self-consistent manner.

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High-resolution gold labeling

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100147491 ◽

1993 ◽

Vol 51 ◽

pp. 330-331

Author(s):

James F. Hainfeld ◽

Frederic R. Furuya ◽

Kyra Carbone ◽

Martha Simon ◽

Beth Lin ◽

...

Keyword(s):

Dihydrofolate Reductase ◽

Polypeptide Chain ◽

External Surface ◽

Gold Cluster ◽

Macromolecular Complex ◽

Gold Compound ◽

Central Cavity ◽

Chain Folding ◽

E Coli ◽

Chaperonin Groel

A recently developed 1.4 nm gold cluster has been found to be useful in labeling macromolecular sites to 1-3 nm resolution. The gold compound is organically derivatized to contain a monofunctional arm for covalent linking to biomolecules. This may be used to mark a specific site on a structure, or to first label a component and then reassemble a multicomponent macromolecular complex. Two examples are given here: the chaperonin groEL and ribosomes.Chaperonins are essential oligomeric complexes that mediate nascent polypeptide chain folding to produce active proteins. The E. coli chaperonin, groEL, has two stacked rings with a central hole ∽6 nm in diameter. The protein dihydrofolate reductase (DHFR) is a small protein that has been used in chain folding experiments, and serves as a model substrate for groEL. By labeling the DHFR with gold, its position with respect to the groEL complex can be followed. In particular, it was sought to determine if DHFR refolds on the external surface of the groEL complex, or whether it interacts in the central cavity.

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Anharmonically-coupled local mode to normal mode Hamiltonian transformations: beyond the x, K-relations

Molecular Physics ◽

10.1080/00268979809482267 ◽

1998 ◽

Vol 93 (5) ◽

pp. 821-830

Author(s):

M.M. LAW ◽

J.L. DUNCAN

Keyword(s):

Normal Mode ◽

Local Mode

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The Nusayris in Medieval Syria

10.23943/princeton/9780691167787.003.0002 ◽

2018 ◽

Author(s):

Stefan Winter

Keyword(s):

Normal Mode ◽

Early Development ◽

A Priori ◽

Medieval Period ◽

Historical Sources

This chapter re-examines the early development of the ʻAlawi community and its situation in western Syria in the medieval period in the wider context of what might be termed Islamic provincial history. It starts from the premise that the conventional image of the “Nusayris” has largely been fashioned by elite historical sources whose discourse on nonorthodox groups is a priori negative but which, when read against the grain and compared with other sources, can yield a less essentializing, less conflicting account of the community's development. In particular, the chapter aims to show that the ʻAlawi faith was not the deviant, marginal phenomenon it has retrospectively been made out to be but, on the contrary, constituted, and was treated by the contemporary authorities as, a normal mode of rural religiosity in Syria.

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