Advances in the study of the mechanochemical coupling of kinesin

2018 ◽  
Vol 32 (18) ◽  
pp. 1840001 ◽  
Author(s):  
Ming Li ◽  
Zhong-Can Ou-Yang ◽  
Yao-Gen Shu
Keyword(s):  
Molecular Dynamics ◽  
Single Molecule ◽  
Intracellular Transport ◽  
Coordination Mechanism ◽  
Personal Perspective ◽  
Long Distance ◽  
Future Studies ◽  
Mechanochemical Coupling ◽  
Dynamics Simulations ◽  
Made In

Kinesin is a two-headed linear motor for intracellular transport. It can walk a long distance in a hand-over-hand manner along the track before detaching (i.e., high processivity), and it consumes one ATP molecule for each step (i.e., tight mechanochemical coupling). The mechanisms of the coordination of its two heads and the mechanochemical coupling are the central issues of numerous researches. A few advances have been made in recent decades, thanks to the development of single-molecule technologies and molecular dynamics simulations. In this paper, we review some progress of the studies on the kinematics, energetics, coordination mechanism, mechanochemical mechanism of kinesin. We also present a personal perspective on the future studies of kinesin.

scholarly journals Multimodal tubulin binding by the yeast kinesin-8, Kip3, underlies its motility and depolymerization

2021 ◽  
Author(s):  
Hugo Arellano-Santoyo ◽  
Rogelio A Hernandez-Lopez ◽  
Emma Stokasimov ◽  
Ray YR Wang ◽  
David Pellman ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Single Molecule ◽  
Conformational Changes ◽  
Intracellular Transport ◽  
Structural Features ◽  
Cellular Processes ◽  
Tubulin Binding ◽  
Dynamics Simulations ◽  
Spatiotemporal Control ◽  
Unique Ability

The microtubule (MT) cytoskeleton is central to cellular processes including axonal growth, intracellular transport, and cell division, all of which rely on precise spatiotemporal control of MT organization. Kinesin-8s play a key role in regulating MT length by combining highly processive directional motility with MT-end disassembly. However, how kinesin-8 switches between these two apparently opposing activities remains unclear. Here, we define the structural features underlying this molecular switch through cryo-EM analysis of the yeast kinesin-8, Kip3 bound to MTs, and molecular dynamics simulations to approximate the complex of Kip3 with the curved tubulin state found at the MT plus-end. By integrating biochemical and single-molecule biophysical assays, we identified specific intra- and intermolecular interactions that modulate processive motility and MT disassembly. Our findings suggest that Kip3 undergoes conformational changes in response to tubulin curvature that underlie its unique ability to interact differently with the MT lattice than with the MT-end.

scholarly journals Molecular dynamics simulations of RNA: Anin silico single molecule approach

Biopolymers ◽  
2007 ◽  
Vol 85 (2) ◽  
pp. 169-184 ◽  
Author(s):  
S. Elizabeth McDowell ◽  
Nad'a Špačková ◽  
Jiří Šponer ◽  
Nils G. Walter
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Single Molecule ◽  
Dynamics Simulations

scholarly journals Breakage of the Oligomeric CaMKII Hub by the Regulatory Segment of the Kinase

2020 ◽  
Author(s):  
Deepti Karandur ◽  
Moitrayee Bhattacharyya ◽  
Beryl Xia ◽  
Young Kwang Lee ◽  
Serena Muratcioglu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Dynamics ◽  
Single Molecule ◽  
Mammalian Cells ◽  
Intensity Analysis ◽  
Single Molecule Fluorescence ◽  
Dependent Protein Kinase ◽  
Large Fluctuations ◽  
Dependent Protein ◽  
Dynamics Simulations

AbstractCa2+/calmodulin dependent protein kinase II (CaMKII) is a dodecameric or tetradecameric enzyme with crucial roles in neuronal signaling and cardiac function. Activation of CaMKII is reported to trigger the exchange of subunits between holoenzymes, which can increase spread of the active state. Using mass spectrometry, we now show that peptides derived from the sequence of the CaMKII-α regulatory segment can bind to the CaMKII-α hub assembly and break it into smaller oligomers. Molecular dynamics simulations show that the regulatory segments can dock spontaneously at the interface between hub subunits, trapping large fluctuations in hub structure. Single-molecule fluorescence intensity analysis of human CaMKII-α isolated from mammalian cells shows that activation of CaMKII-α results in the destabilization of the holoenzyme. Our results show how the release of the regulatory segment by activation and phosphorylation could allow it to destabilize the hub, producing smaller CaMKII assemblies that can reassemble to form new holoenzymes.

scholarly journals Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pairs

2016 ◽  
Author(s):  
Sezen Vatansever ◽  
Zeynep H. Gümüş ◽  
Burak Erman
Keyword(s):  
Molecular Dynamics ◽  
Information Flow ◽  
Analysis Method ◽  
Future Studies ◽  
Correlated Motions ◽  
Novel Approach ◽  
Decay Times ◽  
Dynamics Simulations ◽  
First Time ◽  
Important Therapeutic Target

SummaryWhile mutant K-Ras is an important therapeutic target for human cancers, there are still no drugs that directly target it. Recent promising studies emphasize the significance of dynamics data to selectively target its active/inactive states. However, despite tremendous information on K-Ras, the direction of information flow in the allosteric regulation of its dynamics has not yet been elucidated. Here, we present a novel approach that identifies causality in correlated motions of proteins and apply it to K-Ras dynamics. Specifically, we analyze molecular dynamics simulations data and comprehensively investigate nucleotide-dependent intrinsic K-Ras activity. We show that GTP binding leads to characteristic residue correlations with relatively long decay times by stabilizing K-Ras motions. Furthermore, we identify for the first time driver-follower relationships of correlated motions in the regulation of K-Ras activity. Our results can be utilized for directly targeting mutant K-Ras in future studies.

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