scholarly journals S13H2 ATP hydrolysis-coupled structural changes of the walking molecular motor protein kinesin(Common mechanism found in diversity among various biological motors)

2007 ◽  
Vol 47 (supplement) ◽  
pp. S19
Author(s):  
Michio Tomishige
Keyword(s):  
Structural Changes ◽  
Atp Hydrolysis ◽  
Molecular Motor ◽  
Motor Protein ◽  
Common Mechanism ◽  
Biological Motors

MICROTUBULE-KINESIN MECHANICS BY MOLECULAR MODELING

2009 ◽  
Vol 04 (01n02) ◽  
pp. 45-61 ◽  
Author(s):  
MONICA SONCINI ◽  
EMILIANO VOTTA ◽  
IULIANA APRODU ◽  
SØREN ENEMARK ◽  
ALBERTO REDAELLI ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Molecular Modeling ◽  
Structural Changes ◽  
Atp Hydrolysis ◽  
Interaction Strength ◽  
Motor Protein ◽  
Binding Pocket ◽  
Spatial Distance ◽  
Tubulin Dimer ◽  
Cellular Cytoskeleton

The cellular cytoskeleton contains microtubules which function both as fundamental structural elements as well as motor protein tracks. While the structural property is connected to the properties of the tubulin dimer, its interactions with surrounding dimers and the geometric organization within the microtubule, the transport track properties are related to the interactions between the tubulin dimer and kinesin. Based on the atomistic structures of kinesin and the tubulin dimer, we used molecular modeling to examine the interaction energy and force as function of a spatial distance of separation. From the results, elastic constants describing the system stiffness are obtained. By using the results related to the structure alone, a model of a 1 μm long microtubule is constructed as a network of elastic elements, and its mechanical properties were obtained via finite element method and compared to experimental results. Concerning microtubule-kinesin complex, the interaction strength during a complete cycle of ATP hydrolysis was investigated. As expected, the affinity between the proteins is modulated by the type of nucleotide occupying the nucleotide binding pocket of the motor protein. The work underscores how molecular modeling can provide fundamental protein information in terms of the relation between mechanical properties and structural changes.

scholarly journals Analysis of the Structural Mechanism of ATP Inhibition at the AAA1 Subunit of Cytoplasmic Dynein-1 Using a Chemical “Toolkit”

2021 ◽  
Vol 22 (14) ◽  
pp. 7704
Author(s):  
Sayi’Mone Tati ◽  
Laleh Alisaraie
Keyword(s):  
Binding Affinity ◽  
Atp Hydrolysis ◽  
Critical Role ◽  
Motor Protein ◽  
Structural Data ◽  
Retrograde Transport ◽  
Cytoplasmic Dynein ◽  
Motor Domain ◽  
Conformational Search ◽  
Structural Mechanism

Dynein is a ~1.2 MDa cytoskeletal motor protein that carries organelles via retrograde transport in eukaryotic cells. The motor protein belongs to the ATPase family of proteins associated with diverse cellular activities and plays a critical role in transporting cargoes to the minus end of the microtubules. The motor domain of dynein possesses a hexameric head, where ATP hydrolysis occurs. The presented work analyzes the structure–activity relationship (SAR) of dynapyrazole A and B, as well as ciliobrevin A and D, in their various protonated states and their 46 analogues for their binding in the AAA1 subunit, the leading ATP hydrolytic site of the motor domain. This study exploits in silico methods to look at the analogues’ effects on the functionally essential subsites of the motor domain of dynein 1, since no similar experimental structural data are available. Ciliobrevin and its analogues bind to the ATP motifs of the AAA1, namely, the walker-A (W-A) or P-loop, the walker-B (W-B), and the sensor I and II. Ciliobrevin A shows a better binding affinity than its D analogue. Although the double bond in ciliobrevin A and D was expected to decrease the ligand potency, they show a better affinity to the AAA1 binding site than dynapyrazole A and B, lacking the bond. In addition, protonation of the nitrogen atom in ciliobrevin A and D, as well as dynapyrazole A and B, at the N9 site of ciliobrevin and the N7 of the latter increased their binding affinity. Exploring ciliobrevin A geometrical configuration suggests the E isomer has a superior binding profile over the Z due to binding at the critical ATP motifs. Utilizing the refined structure of the motor domain obtained through protein conformational search in this study exhibits that Arg1852 of the yeast cytoplasmic dynein could involve in the “glutamate switch” mechanism in cytoplasmic dynein 1 in lieu of the conserved Asn in AAA+ protein family.

scholarly journals Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and Pi Release

2020 ◽  
Vol 22 (1) ◽  
pp. 104
Author(s):  
Peter Franz ◽  
Wiebke Ewert ◽  
Matthias Preller ◽  
Georgios Tsiavaliaris
Keyword(s):  
Structural Changes ◽  
Atp Hydrolysis ◽  
Power Stroke ◽  
Duty Ratio ◽  
Prolonged Duration ◽  
Adp Release ◽  
Strong Transition ◽  
Cleft Closure ◽  
Kinetic Investigations ◽  
Allosteric Pathway

The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.

scholarly journals Motif V regulates energy transduction between the flavivirus NS3 ATPase and RNA-binding cleft

2019 ◽  
Vol 295 (6) ◽  
pp. 1551-1564 ◽  
Author(s):  
Kelly E. Du Pont ◽  
Russell B. Davidson ◽  
Martin McCullagh ◽  
Brian J. Geiss
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Rna Binding ◽  
Atp Hydrolysis ◽  
Nonstructural Protein ◽  
Binding Pocket ◽  
Energy Transduction ◽  
Helicase Domain ◽  
Genome Replication ◽  
Turnover Rates

The unwinding of dsRNA intermediates is critical for the replication of flavivirus RNA genomes. This activity is provided by the C-terminal helicase domain of viral nonstructural protein 3 (NS3). As a member of the superfamily 2 (SF2) helicases, NS3 requires the binding and hydrolysis of ATP/NTP to translocate along and unwind double-stranded nucleic acids. However, the mechanism of energy transduction between the ATP- and RNA-binding pockets is not well-understood. Previous molecular dynamics simulations conducted by our group have identified Motif V as a potential “communication hub” for this energy transduction pathway. To investigate the role of Motif V in this process, here we combined molecular dynamics, biochemistry, and virology approaches. We tested Motif V mutations in both the replicon and recombinant protein systems to investigate viral genome replication, RNA-binding affinity, ATP hydrolysis activity, and helicase-mediated unwinding activity. We found that the T407A and S411A substitutions in NS3 reduce viral replication and increase the helicase-unwinding turnover rates by 1.7- and 3.5-fold, respectively, suggesting that flaviviruses may use suboptimal NS3 helicase activity for optimal genome replication. Additionally, we used simulations of each mutant to probe structural changes within NS3 caused by each mutation. These simulations indicate that Motif V controls communication between the ATP-binding pocket and the helical gate. These results help define the linkage between ATP hydrolysis and helicase activities within NS3 and provide insight into the biophysical mechanisms for ATPase-driven NS3 helicase function.

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

scholarly journals Molecular motor protein KIF5C mediates structural plasticity and long-term memory by constraining local translation

Cell Reports ◽  
2021 ◽  
Vol 36 (2) ◽  
pp. 109369
Author(s):  
Supriya Swarnkar ◽  
Yosef Avchalumov ◽  
Isabel Espadas ◽  
Eddie Grinman ◽  
Xin-an Liu ◽  
...  
Keyword(s):  
Molecular Motor ◽  
Motor Protein ◽  
Structural Plasticity ◽  
Long Term Memory ◽  
Local Translation ◽  
Term Memory

scholarly journals Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase

2018 ◽  
Vol 115 (43) ◽  
pp. E10041-E10048 ◽  
Author(s):  
J. Brooks Crickard ◽  
Kyle Kaniecki ◽  
Youngho Kwon ◽  
Patrick Sung ◽  
Eric C. Greene
Keyword(s):  
Chromosome Segregation ◽  
Single Molecule ◽  
Atp Hydrolysis ◽  
Potent Inhibitor ◽  
Chromosomal Rearrangements ◽  
Motor Protein ◽  
Product Formation ◽  
Gross Chromosomal Rearrangements ◽  
Strand Annealing ◽  
Hydrolysis Activity

Cross-over recombination products are a hallmark of meiosis because they are necessary for accurate chromosome segregation and they also allow for increased genetic diversity during sexual reproduction. However, cross-overs can also cause gross chromosomal rearrangements and are therefore normally down-regulated during mitotic growth. The mechanisms that enhance cross-over product formation upon entry into meiosis remain poorly understood. In Saccharomyces cerevisiae, the Superfamily 1 (Sf1) helicase Srs2, which is an ATP hydrolysis-dependent motor protein that actively dismantles recombination intermediates, promotes synthesis-dependent strand annealing, the result of which is a reduction in cross-over recombination products. Here, we show that the meiosis-specific recombinase Dmc1 is a potent inhibitor of Srs2. Biochemical and single-molecule assays demonstrate that Dmc1 acts by inhibiting Srs2 ATP hydrolysis activity, which prevents the motor protein from undergoing ATP hydrolysis-dependent translocation on Dmc1-bound recombination intermediates. We propose a model in which Dmc1 helps contribute to cross-over formation during meiosis by antagonizing the antirecombinase activity of Srs2.

scholarly journals Origin of the enhanced structural and reorientational relaxation rates in the presence of relatively weak dc electric fields

2004 ◽  
Vol 76 (1) ◽  
pp. 215-221 ◽  
Author(s):  
A. Vegiri
Keyword(s):  
Molecular Dynamics ◽  
Electric Field ◽  
Electric Fields ◽  
Structural Relaxation ◽  
Structural Changes ◽  
Common Mechanism ◽  
Weak Electric Field ◽  
Water Molecules ◽  
Relaxation Rates ◽  
Dynamics Simulations

The origin of the dramatic increase of the reorientational and structural relaxation rates of single water molecules in clusters of size N = 16, 32, and 64 at T = 200 K, under the influence of an external, relatively weak electric field (~0.5 107 V/cm) is examined through molecular dynamics simulations. The observed effect is attributed not to any profound structural changes, but to the increase of the size of the molecular cage. The response of water to an electric field in this range shows many similarities with the dynamics of water under low pressure. By referring to simulations and experiments from the literature, we show that in both cases the observed effects are dictated by a common mechanism.

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