scholarly journals How Kinesin-1 Utilize the Energy of Nucleotide: The Conformational Changes and Mechanochemical Coupling in the Unidirectional Motion of Kinesin-1

2020 ◽  
Vol 21 (18) ◽  
pp. 6977
Author(s):  
Jingyu Qin ◽  
Hui Zhang ◽  
Yizhao Geng ◽  
Qing Ji
Keyword(s):  
Conformational Changes ◽  
Molecular Motor ◽  
Energy Transition ◽  
Significant Feature ◽  
Nucleotide Hydrolysis ◽  
Mechanochemical Coupling ◽  
Mechanochemical Cycle ◽  
Mechanical Movement ◽  
Kinesin Family ◽  
Unidirectional Motion

Kinesin-1 is a typical motile molecular motor and the founding member of the kinesin family. The most significant feature in the unidirectional motion of kinesin-1 is its processivity. To realize the fast and processive movement on the microtubule lattice, kinesin-1 efficiently transforms the chemical energy of nucleotide binding and hydrolysis to the energy of mechanical movement. The chemical and mechanical cycle of kinesin-1 are coupled to avoid futile nucleotide hydrolysis. In this paper, the research on the mechanical pathway of energy transition and the regulating mechanism of the mechanochemical cycle of kinesin-1 is reviewed.

scholarly journals F1-ATPase conformational cycle from simultaneous single-molecule FRET and rotation measurements

2016 ◽  
Vol 113 (21) ◽  
pp. E2916-E2924 ◽  
Author(s):  
Mitsuhiro Sugawa ◽  
Kei-ichi Okazaki ◽  
Masaru Kobayashi ◽  
Takashi Matsui ◽  
Gerhard Hummer ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Single Molecule ◽  
Conformational Changes ◽  
Molecular Motor ◽  
Principal Component ◽  
Structural Basis ◽  
F1 Atpase ◽  
Single Molecule Fret ◽  
Mechanochemical Coupling ◽  
Central Shaft

Despite extensive studies, the structural basis for the mechanochemical coupling in the rotary molecular motor F1-ATPase (F1) is still incomplete. We performed single-molecule FRET measurements to monitor conformational changes in the stator ring-α3β3, while simultaneously monitoring rotations of the central shaft-γ. In the ATP waiting dwell, two of three β-subunits simultaneously adopt low FRET nonclosed forms. By contrast, in the catalytic intermediate dwell, two β-subunits are simultaneously in a high FRET closed form. These differences allow us to assign crystal structures directly to both major dwell states, thus resolving a long-standing issue and establishing a firm connection between F1 structure and the rotation angle of the motor. Remarkably, a structure of F1 in an ε-inhibited state is consistent with the unique FRET signature of the ATP waiting dwell, while most crystal structures capture the structure in the catalytic dwell. Principal component analysis of the available crystal structures further clarifies the five-step conformational transitions of the αβ-dimer in the ATPase cycle, highlighting the two dominant modes: the opening/closing motions of β and the loosening/tightening motions at the αβ-interface. These results provide a new view of tripartite coupling among chemical reactions, stator conformations, and rotary angles in F1-ATPase.

scholarly journals Studies of Conformational Changes of Tubulin Induced by Interaction with Kinesin Using Atomistic Molecular Dynamics Simulations

2021 ◽  
Vol 22 (13) ◽  
pp. 6709
Author(s):  
Xiao-Xuan Shi ◽  
Peng-Ye Wang ◽  
Hong Chen ◽  
Ping Xie
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Binding Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Weak Interactions ◽  
Molecular Motor ◽  
Structural Data ◽  
Calculated Binding Energy ◽  
Dynamics Simulations

The transition between strong and weak interactions of the kinesin head with the microtubule, which is regulated by the change of the nucleotide state of the head, is indispensable for the processive motion of the kinesin molecular motor on the microtubule. Here, using all-atom molecular dynamics simulations, the interactions between the kinesin head and tubulin are studied on the basis of the available high-resolution structural data. We found that the strong interaction can induce rapid large conformational changes of the tubulin, whereas the weak interaction cannot. Furthermore, we found that the large conformational changes of the tubulin have a significant effect on the interaction of the tubulin with the head in the weak-microtubule-binding ADP state. The calculated binding energy of the ADP-bound head to the tubulin with the large conformational changes is only about half that of the tubulin without the conformational changes.

scholarly journals A FRET-Based Sensor Reveals Large ATP Hydrolysis–Induced Conformational Changes and Three Distinct States of the Molecular Motor Myosin

Cell ◽  
2000 ◽  
Vol 102 (5) ◽  
pp. 683-694 ◽  
Author(s):  
William M Shih ◽  
Zygmunt Gryczynski ◽  
Joseph R Lakowicz ◽  
James A Spudich
Keyword(s):  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Molecular Motor

A hemithioindigo molecular motor for metal surface attachment

2019 ◽  
Vol 17 (7) ◽  
pp. 1979-1983 ◽  
Author(s):  
Kerstin Hoffmann ◽  
Peter Mayer ◽  
Henry Dube
Keyword(s):  
Metal Surface ◽  
Molecular Motor ◽  
Surface Attachment ◽  
Unidirectional Motion ◽  
Comprehensive Study ◽  
Motor Bearing

We report on the synthesis of a hemithioindigo molecular motor bearing thioether feet for metal surface attachment and a comprehensive study of its light induced unidirectional motion in solution.

scholarly journals X-ray and cryo-EM structures of monomeric and filamentous actin-like protein MamK reveal changes associated with polymerization

2016 ◽  
Vol 113 (47) ◽  
pp. 13396-13401 ◽  
Author(s):  
Jan Löwe ◽  
Shaoda He ◽  
Sjors H. W. Scheres ◽  
Christos G. Savva
Keyword(s):  
Conformational Changes ◽  
Magnetic Moments ◽  
Magnetotactic Bacteria ◽  
Binding Pocket ◽  
Filamentous Actin ◽  
Nucleotide Hydrolysis ◽  
Filamentous Form ◽  
Domain Movement ◽  
Density Map ◽  
Magnetospirillum Magneticum

Magnetotactic bacteria produce iron-rich magnetic nanoparticles that are enclosed by membrane invaginations to form magnetosomes so they are able to sense and act upon Earth’s magnetic field. In Magnetospirillum and other magnetotactic bacteria, to combine their magnetic moments, magnetosomes align along filaments formed by a bacterial actin homolog, MamK. Here, we present the crystal structure of a nonpolymerizing mutant of MamK from Magnetospirillum magneticum AMB-1 at 1.8-Å resolution, revealing its close similarity to actin and MreB. The crystals contain AMPPNP-bound monomeric MamK in two different conformations. To investigate conformational changes associated with polymerization, we used unmodified MamK protein and cryo-EM with helical 3D reconstruction in RELION to obtain a density map and a fully refined atomic model of MamK in filamentous form at 3.6-Å resolution. The filament is parallel (polar) double-helical, with a rise of 52.2 Å and a twist of 23.8°. As shown previously and unusually for actin-like filaments, the MamK subunits from each of the two strands are juxtaposed, creating an additional twofold axis along the filament. Compared with monomeric MamK, ADP-bound MamK in the filament undergoes a conformational change, rotating domains I and II against each other to further close the interdomain cleft between subdomains IB and IIB. The domain movement causes several loops to close around the nucleotide-binding pocket. Glu-143, a key residue for catalysis coordinating the magnesium ion, moves closer, presumably switching nucleotide hydrolysis upon polymerization—one of the hallmarks of cytomotive filaments of the actin type.

scholarly journals RNA Packaging Motor: From Structure to Quantum Mechanical Modelling and Sequential-Stochastic Mechanism

2008 ◽  
Vol 9 (3-4) ◽  
pp. 351-369 ◽  
Author(s):  
Jelena Telenius ◽  
Anders E. Wallin ◽  
Michal Straka ◽  
Hongbo Zhang ◽  
Erika J. Mancini ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Atp Hydrolysis ◽  
Structural Information ◽  
Molecular Motor ◽  
Structural Similarity ◽  
Binding Pocket ◽  
Reaction Coordinate ◽  
Rna Packaging ◽  
Cooperative Action ◽  
Empty Capsid

The bacteriophages of theCystoviridaefamily package their single stranded RNA genomic precursors into empty capsid (procapsids) using a hexameric packaging ATPase motor (P4). This molecular motor shares sequence and structural similarity with RecA-like hexameric helicases. A concerted structural, mutational and kinetic analysis helped to define the mechanical reaction coordinate,i.e.the conformational changes associated with RNA translocation. The results also allowed us to propose a possible scheme of coupling between ATP hydrolysis and translocation which requires the cooperative action of three consecutive subunits. Here, we first test this model by preparing hexamers with defined proportions of wild type and mutant subunits and measuring their activity. Then, we develop a stochastic kinetic model which accounts for the catalytic cooperativity of the P4 hexamer. Finally, we use the available structural information to construct a quantum-chemical model of the chemical reaction coordinate and obtain a detailed description of the electron density changes during ATP hydrolysis. The model explains the results of the mutational analyses and yields new insights into the role of several conserved residues within the ATP binding pocket. These hypotheses will guide future experimental work.

scholarly journals Mechanism of FtsZ assembly dynamics revealed by filament structures in different nucleotide states

2021 ◽  
Author(s):  
Federico M. Ruiz ◽  
Sonia Huecas ◽  
Alicia Santos-Aledo ◽  
Elena A. Prim ◽  
José M. Andreu ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Active Site ◽  
Mechanistic Model ◽  
Bacterial Cell Division ◽  
Cellular Functions ◽  
Nucleotide Hydrolysis ◽  
Subunit Interface ◽  
Water Shell ◽  
Biochemical Analyses ◽  
Ftsz Assembly

Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogues and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg2+ at the subunit interface, a K+ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signalling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.

scholarly journals Computational Tool for Ensemble Averaging of Single-Molecule Data

2020 ◽  
Author(s):  
Thomas Blackwell ◽  
W. Tom Stump ◽  
Sarah R. Clippinger ◽  
Michael J. Greenberg
Keyword(s):  
Brownian Motion ◽  
User Interface ◽  
Single Molecule ◽  
Conformational Changes ◽  
Graphical User Interface ◽  
Molecular Motions ◽  
Computational Tool ◽  
Ensemble Averaging ◽  
Mechanochemical Coupling ◽  
Kinetics Of

AbstractMolecular motors couple chemical transitions to conformational changes that perform mechanical work in a wide variety of biological processes. Disruption of this coupling can lead to diseases, and therefore there is a need to accurately measure mechanochemical coupling in motors in both health and disease. Optical tweezers, with nanometer spatial and millisecond temporal resolution, have provided valuable insights into these processes. However, fluctuations due to Brownian motion can make it difficult to precisely resolve these conformational changes. One powerful analysis technique that has improved our ability to accurately measure mechanochemical coupling in motor proteins is ensemble averaging of individual trajectories. Here, we present a user-friendly computational tool, Software for Precise Analysis of Single Molecules (SPASM), for generating ensemble averages of single-molecule data. This tool utilizes several conceptual advances, including optimized procedures for identifying single-molecule interactions and the implementation of a change point algorithm, to more precisely resolve molecular transitions. Using both simulated and experimental data, we demonstrate that these advances allow for accurate determination of the mechanics and kinetics of the myosin working stroke with a smaller set of data. Importantly, we provide our open source MATLAB-based program with a graphical user interface that enables others to readily apply these advances to the analysis of their own data.Statement of SignificanceSingle molecule optical trapping experiments have given unprecedented insights into the mechanisms of molecular machines. Analysis of these experiments is often challenging because Brownian motion-induced fluctuations introduce noise that can obscure molecular motions. A powerful technique for analyzing these noisy traces is ensemble averaging of individual binding interactions, which can uncover information about the mechanics and kinetics of molecular motions that are typically obscured by Brownian motion. Here, we provide an open source, easy-to-use computational tool, SPASM, with a graphical user interface for ensemble averaging of single molecule data. This computational tool utilizes several conceptual advances that significantly improve the accuracy and resolution of ensemble averages, enabling the generation of high-resolution averages from a smaller number of binding interactions.

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