scholarly journals Initiation of ensemble kinesin-3 motility is regulated by the rigidity of cargo-motor attachment

2021 ◽  
Author(s):  
Prakash Lama ◽  
Minhajuddin Sirajuddin
Keyword(s):  
Atpase Activity ◽  
Molecular Motors ◽  
Coiled Coils ◽  
Dna Origami ◽  
Degree Of Freedom ◽  
Double Stranded Dna ◽  
Cargo Transport ◽  
Regulatory Effects

AbstractIntracellular cargo transport is powered by molecular motors that move on their respective filamentous tracks. A key component in this process is the tether between cargo and motor, which is often connected by long slender coiled-coils. Several studies have identified mechanisms that regulate cargo transport and can be broadly categorized into regulation of the motor ATPase activity by autoinhibition, cargo adapters and modifications in the cytoskeletal tracks. The regulatory effects of cargo-motor linkers have been described in kinesin-3 subfamily motors. However, the effects of cargo-motor linker rigidity on ensemble cargo transport has not been explored. Here we have built a DNA origami scaffold, which can be tethered with multiple kinesin-3 motors using either single or double-stranded DNA linkages, mimicking rigid versus flexible cargo-motor linkages. Using this system, we show that regardless of the motor numbers attached to the cargo, only linkers with a lesser degree of freedom allow motors to engage with microtubule tracks. Together, our work identifies that the rigidity of cargo-motor linkages influences motor motility. This opens up the possibilities to identify new factors that can influence the rigidity of cargo-motor linkages that in turn can regulate intracellular cargo transport.

scholarly journals Stochastic Modeling of Cargo Transport by Teams of Molecular Motors

2014 ◽  
pp. 609-617
Author(s):  
Sarah Klein ◽  
Cécile Appert-Rolland ◽  
Ludger Santen
Keyword(s):  
Stochastic Modeling ◽  
Molecular Motors ◽  
Cargo Transport

scholarly journals An automated in vitro motility assay for high-throughput studies of molecular motors

Lab on a Chip ◽  
2018 ◽  
Vol 18 (20) ◽  
pp. 3196-3206 ◽  
Author(s):  
Till Korten ◽  
Elena Tavkin ◽  
Lara Scharrel ◽  
Vandana Singh Kushwaha ◽  
Stefan Diez
Keyword(s):  
High Throughput ◽  
Molecular Motors ◽  
Lab On A Chip ◽  
Force Generation ◽  
Motility Assay ◽  
In Vitro Motility Assay ◽  
In Vitro Motility ◽  
Cargo Transport

Molecular motors, essential to force-generation and cargo transport within cells, are invaluable tools for powering nanobiotechnological lab-on-a-chip devices.

scholarly journals DNA Origami Nanomachines

Molecules ◽  
2018 ◽  
Vol 23 (7) ◽  
pp. 1766 ◽  
Author(s):  
Masayuki Endo ◽  
Hiroshi Sugiyama
Keyword(s):  
Dna Sequences ◽  
Molecular Motors ◽  
Molecular Machines ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Molecular Systems ◽  
Nanoscale Structures ◽  
Research Fields ◽  
Dna Strands ◽  
External Stimuli

DNA can assemble various molecules and nanomaterials in a programmed fashion and is a powerful tool in the nanotechnology and biology research fields. DNA also allows the construction of desired nanoscale structures via the design of DNA sequences. Structural nanotechnology, especially DNA origami, is widely used to design and create functionalized nanostructures and devices. In addition, DNA molecular machines have been created and are operated by specific DNA strands and external stimuli to perform linear, rotational, and reciprocating movements. Furthermore, complicated molecular systems have been created on DNA nanostructures by arranging multiple molecules and molecular machines precisely to mimic biological systems. Currently, DNA nanomachines, such as molecular motors, are operated on DNA nanostructures. Dynamic DNA nanostructures that have a mechanically controllable system have also been developed. In this review, we describe recent research on new DNA nanomachines and nanosystems that were built on designed DNA nanostructures.

scholarly journals Force Dependence of Velocity and Run Length of Kinesin-1, Kinesin-2 and Kinesin-5 Family Molecular Motors

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 287 ◽  
Author(s):  
Si-Kao Guo ◽  
Wei-Chi Wang ◽  
Peng-Ye Wang ◽  
Ping Xie
Keyword(s):  
Experimental Data ◽  
Atpase Activity ◽  
Rate Constants ◽  
Molecular Motors ◽  
Quantitative Agreement ◽  
Run Length ◽  
Movement Dynamics ◽  
Proposed Model ◽  
Movement Mechanism ◽  
The Difference

Kinesin-1, kinesin-2 and kinesin-5 are three families of a superfamily of motor proteins; which can walk processively on microtubule filaments by hydrolyzing ATP. It was experimentally shown that while the three kinesin dimers show similar feature on the force dependence of velocity, they show rather different features on the force dependence of run length. However, why the three families of kinesins show these rather different features is unclear. Here, we computationally studied the movement dynamics of the three dimers based on our proposed model. The simulated results reproduce well the available experimental data on the force dependence of velocity and run length. Moreover, the simulated results on the velocity and run length for the three dimers with altered neck linker lengths are also in quantitative agreement with the available experimental data. The studies indicate that the three families of kinesins show much similar movement mechanism and the rather different features on the force dependence of run length arise mainly from the difference in rate constants of the ATPase activity and neck linker docking. Additionally, the asymmetric (limping) movement dynamics of the three families of homodimers with and without altered neck linker lengths are studied, providing predicted results.

scholarly journals Single-molecule visualization of human BLM helicase as it acts upon double- and single-stranded DNA substrates

2019 ◽  
Vol 47 (21) ◽  
pp. 11225-11237 ◽  
Author(s):  
Chaoyou Xue ◽  
James M Daley ◽  
Xiaoyu Xue ◽  
Justin Steinfeld ◽  
Youngho Kwon ◽  
...  
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Genetic Disorder ◽  
Protein A ◽  
Base Pairs ◽  
Single Stranded Dna ◽  
Double Stranded Dna ◽  
Blm Helicase ◽  
Dna Replication And Repair ◽  
Regulatory Effects

Abstract Bloom helicase (BLM) and its orthologs are essential for the maintenance of genome integrity. BLM defects represent the underlying cause of Bloom Syndrome, a rare genetic disorder that is marked by strong cancer predisposition. BLM deficient cells accumulate extensive chromosomal aberrations stemming from dysfunctions in homologous recombination (HR). BLM participates in several HR stages and helps dismantle potentially harmful HR intermediates. However, much remains to be learned about the molecular mechanisms of these BLM-mediated regulatory effects. Here, we use DNA curtains to directly visualize the activity of BLM helicase on single molecules of DNA. Our data show that BLM is a robust helicase capable of rapidly (∼70–80 base pairs per second) unwinding extensive tracts (∼8–10 kilobases) of double-stranded DNA (dsDNA). Importantly, we find no evidence for BLM activity on single-stranded DNA (ssDNA) that is bound by replication protein A (RPA). Likewise, our results show that BLM can neither associate with nor translocate on ssDNA that is bound by the recombinase protein RAD51. Moreover, our data reveal that the presence of RAD51 also blocks BLM translocation on dsDNA substrates. We discuss our findings within the context of potential regulator roles for BLM helicase during DNA replication and repair.

scholarly journals A Generalized Kinetic Model for Coupling between Stepping and ATP Hydrolysis of Kinesin Molecular Motors

2019 ◽  
Vol 20 (19) ◽  
pp. 4911 ◽  
Author(s):  
Xie ◽  
Guo ◽  
Chen
Keyword(s):  
Kinetic Model ◽  
Atpase Activity ◽  
Single Molecule ◽  
Rate Constants ◽  
Molecular Motors ◽  
Atp Hydrolysis ◽  
Power Production ◽  
Wild Type ◽  
Chemomechanical Coupling ◽  
Generalized Kinetic Model

A general kinetic model is presented for the chemomechanical coupling of dimeric kinesin molecular motors with and without extension of their neck linkers (NLs). A peculiar feature of the model is that the rate constants of ATPase activity of a kinesin head are independent of the strain on its NL, implying that the heads of the wild-type kinesin dimer and the mutant with extension of its NLs have the same force-independent rate constants of the ATPase activity. Based on the model, an analytical theory is presented on the force dependence of the dynamics of kinesin dimers with and without extension of their NLs at saturating ATP. With only a few adjustable parameters, diverse available single molecule data on the dynamics of various kinesin dimers, such as wild-type kinesin-1, kinesin-1 with mutated residues in the NLs, kinesin-1 with extension of the NLs and wild-type kinesin-2, under varying force and ATP concentration, can be reproduced very well. Additionally, we compare the power production among different kinesin dimers, showing that the mutation in the NLs reduces the power production and the extension of the NLs further reduces the power production.

External forces influence the elastic coupling effects during cargo transport by molecular motors

2015 ◽  
Vol 91 (2) ◽  
Author(s):  
Florian Berger ◽  
Corina Keller ◽  
Stefan Klumpp ◽  
Reinhard Lipowsky
Keyword(s):  
Molecular Motors ◽  
Elastic Coupling ◽  
Coupling Effects ◽  
Cargo Transport ◽  
External Forces

scholarly journals COOPERATIVE TRANSPORT BY SMALL TEAMS OF MOLECULAR MOTORS

2006 ◽  
Vol 01 (04) ◽  
pp. 353-361 ◽  
Author(s):  
STEFAN KLUMPP ◽  
MELANIE J. I. MÜLLER ◽  
REINHARD LIPOWSKY
Keyword(s):  
Molecular Motors ◽  
Single Motor ◽  
Directed Transport ◽  
Cargo Transport ◽  
Cooperative Transport

Molecular motors power directed transport of cargoes within cells. Even if a single motor is sufficient to transport a cargo, motors often cooperate in small teams. We discuss the cooperative cargo transport by several motors theoretically and explore some of its properties. In particular we emphasize how motor teams can drag cargoes through a viscous environment.

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