scholarly journals Different degrees of lever arm rotation control myosin step size

2003 ◽  
Vol 161 (2) ◽  
pp. 237-241 ◽  
Author(s):  
Danny Köhler ◽  
Christine Ruff ◽  
Edgar Meyhöfer ◽  
Martin Bähler
Keyword(s):  
Light Chain ◽  
Structural Changes ◽  
Quantitative Agreement ◽  
Linear Increase ◽  
Binding Domain ◽  
Motor Domain ◽  
Step Size ◽  
The Core ◽  
Lever Arm ◽  
Head Domain

Myosins are actin-based motors that are generally believed to move by amplifying small structural changes in the core motor domain via a lever arm rotation of the light chain binding domain. However, the lack of a quantitative agreement between observed step sizes and the length of the proposed lever arms from different myosins challenges this view. We analyzed the step size of rat myosin 1d (Myo1d) and surprisingly found that this myosin takes unexpectedly large steps in comparison to other myosins. Engineering the length of the light chain binding domain of rat Myo1d resulted in a linear increase of step size in relation to the putative lever arm length, indicative of a lever arm rotation of the light chain binding domain. The extrapolated pivoting point resided in the same region of the rat Myo1d head domain as in conventional myosins. Therefore, rat Myo1d achieves its larger working stroke by a large calculated ∼90° rotation of the light chain binding domain. These results demonstrate that differences in myosin step sizes are not only controlled by lever arm length, but also by substantial differences in the degree of lever arm rotation.

scholarly journals Kinematics of the lever arm swing in myosin VI

2017 ◽  
Vol 114 (22) ◽  
pp. E4389-E4398 ◽  
Author(s):  
Mauro L. Mugnai ◽  
D. Thirumalai
Keyword(s):  
Rotational Diffusion ◽  
Quantitative Agreement ◽  
Motor Domain ◽  
Coarse Grained ◽  
Power Stroke ◽  
Myosin Vi ◽  
Step Size ◽  
Arm Swing ◽  
Coarse Grained Model ◽  
Lever Arm

Myosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively toward the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a unique coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps. First, the motor domain attains the poststroke conformation without directing the lever arm forward; and second, the lever arm reaches the poststroke orientation by undergoing a rotational diffusion. From the analysis of the trajectories, we discover that the potential that directs the rotating lever arm toward the poststroke conformation is almost flat, implying that the lever arm rotation is mostly uncoupled from the motor domain. Because a backward load comparable to the largest interhead tension in a MVI dimer prevents the rotation of the lever arm, our model suggests that the leading-head lever arm of a MVI dimer is uncoupled, in accord with the inference drawn from polarized total internal reflection fluorescence (polTIRF) experiments. Without any adjustable parameter, our simulations lead to quantitative agreement with polTIRF experiments, which validates the structural insights. Finally, in addition to making testable predictions, we also discuss the implications of our model in explaining the broad step-size distribution of the MVI stepping pattern.

scholarly journals Kinematics of the Lever Arm Swing in Myosin VI

2016 ◽  
Author(s):  
M. L. Mugnai ◽  
D. Thirumalai
Keyword(s):  
Rotational Diffusion ◽  
Quantitative Agreement ◽  
Motor Domain ◽  
Coarse Grained ◽  
Power Stroke ◽  
Myosin Vi ◽  
Step Size ◽  
Arm Swing ◽  
Post Stroke ◽  
Lever Arm

AbstractMyosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively towards the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a new coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps: first, the motor domain attains the post-stroke conformation without directing the lever arm forward; second, the lever arm reaches the post-stroke orientation by undergoing a rotational diffusion. From the analysis of the trajectories, we discover that the potential that directs the rotating lever arm towards the post-stroke conformation is almost flat, implying that the lever arm rotation is mostly un-coupled from the motor domain. Because a backward load comparable with the largest inter-head tension in a MVI dimer prevents the rotation of the lever arm, our model suggests that the leading-head lever arm of a MVI dimer is uncoupled, in accord with the inference drawn from polarized Total Internal Reflection Fluorescence (polTIRF) experiments. Our simulations are in quantitative agreement with polTIRF experiments, which validates our structural insights. Finally, we discuss the implications of our model in explaining the broad step-size distribution of MVI stepping pattern, and we make testable predictions.

scholarly journals Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin

2020 ◽  
Vol 120 (12) ◽  
pp. 1700-1715
Author(s):  
Courtney J. Mycroft-West ◽  
Dunhao Su ◽  
Isabel Pagani ◽  
Timothy R. Rudd ◽  
Stefano Elli ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Changes ◽  
Rapid Development ◽  
Antiviral Agents ◽  
Vero Cells ◽  
Binding Domain ◽  
Microbial Pathogens ◽  
Minimum Size ◽  
Structural Basis ◽  
Receptor Binding Domain

AbstractThe dependence of development and homeostasis in animals on the interaction of hundreds of extracellular regulatory proteins with the peri- and extracellular glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means of adherence and invasion. Heparin, a widely used anticoagulant drug, is structurally similar to HS and is a common experimental proxy. Exogenous heparin prevents infection by a range of viruses, including S-associated coronavirus isolate HSR1. Here, we show that heparin inhibits severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) invasion of Vero cells by up to 80% at doses achievable through prophylaxis and, particularly relevant, within the range deliverable by nebulisation. Surface plasmon resonance and circular dichroism spectroscopy demonstrate that heparin and enoxaparin, a low-molecular-weight heparin which is a clinical anticoagulant, bind and induce a conformational change in the spike (S1) protein receptor-binding domain (S1 RBD) of SARS-CoV-2. A library of heparin derivatives and size-defined fragments were used to probe the structural basis of this interaction. Binding to the RBD is more strongly dependent on the presence of 2-O or 6-O sulfate groups than on N-sulfation and a hexasaccharide is the minimum size required for secondary structural changes to be induced in the RBD. It is likely that inhibition of viral infection arises from an overlap between the binding sites of heparin/HS on S1 RBD and that of the angiotensin-converting enzyme 2. The results suggest a route for the rapid development of a first-line therapeutic by repurposing heparin and its derivatives as antiviral agents against SARS-CoV-2 and other members of the Coronaviridae.

Structural changes induced by cation ordering in ferrotapiolite

2006 ◽  
Vol 70 (3) ◽  
pp. 319-328 ◽  
Author(s):  
M. Zema ◽  
S.C. Tarantino ◽  
A. Giorgiani
Keyword(s):  
Structural Changes ◽  
Rapid Determination ◽  
Linear Increase ◽  
X Ray Diffraction ◽  
Ionic Radii ◽  
Structural Modifications ◽  
Lattice Constants ◽  
Structure Factors ◽  
Polyhedral Volumes ◽  
Degree Of Order

AbstractStructural modifications as a function of the degree of order (Q) in FeTa2O6 ferrotapiolite have been characterized by means of single-crystal X-ray diffraction (SC-XRD). A total of 26 datasets covering the range of Q between 0.154 and 1 have been obtained by thermal treatments followed by quenching of natural tapiolite crystals. Ordering of Fe2+ at the A sites and of Ta5+ at the B sites causes a linear increase in the a/c lattice constants ratio, as a consequence of a linear decrease of the c dimension and only slight modifications of the a parameter. Calibration of a/c vs. Q represents a very useful tool for a rapid determination of the degree of order of tapiolite samples. Polyhedral volumes of the two octahedral sites vary linearly with Q as a consequence of the different ionic radii of the two species. Both the sites remain almost regular at all Q values but the B site shows an increasing off-centre displacement of the cation with increasing Q. Observed structure factors of supercell reflections, characterized by l ≠ 3n, increase linearly as a function of Q, thus representing a further tool for a quick evaluation of the degree of order.

scholarly journals Regulatory Light Chain Mutants Linked to Heart Disease Modify the Cardiac Myosin Lever Arm

Biochemistry ◽  
2013 ◽  
Vol 52 (7) ◽  
pp. 1249-1259 ◽  
Author(s):  
Thomas P. Burghardt ◽  
Laura A. Sikkink
Keyword(s):  
Heart Disease ◽  
Light Chain ◽  
Regulatory Light Chain ◽  
Cardiac Myosin ◽  
Lever Arm

scholarly journals Assembly of T-Antigen Double Hexamers on the Simian Virus 40 Core Origin Requires Only a Subset of the Available Binding Sites

1998 ◽  
Vol 18 (5) ◽  
pp. 2677-2687 ◽  
Author(s):  
Woo S. Joo ◽  
Henry Y. Kim ◽  
John D. Purviance ◽  
K. R. Sreekumar ◽  
Peter A. Bullock
Keyword(s):  
Structural Changes ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Wild Type ◽  
The Core ◽  
Structural Distortions ◽  
In The Wild ◽  
Sv40 Dna ◽  
Initial Assembly

ABSTRACT Initiation of simian virus 40 (SV40) DNA replication is dependent upon the assembly of two T-antigen (T-ag) hexamers on the SV40 core origin. To further define the oligomerization mechanism, the pentanucleotide requirements for T-ag assembly were investigated. Here, we demonstrate that individual pentanucleotides support hexamer formation, while particular pairs of pentanucleotides suffice for the assembly of T-ag double hexamers. Related studies demonstrate that T-ag double hexamers formed on “active pairs” of pentanucleotides catalyze a set of previously described structural distortions within the core origin. For the four-pentanucleotide-containing wild-type SV40 core origin, footprinting experiments indicate that T-ag double hexamers prefer to bind to pentanucleotides 1 and 3. Collectively, these experiments demonstrate that only two of the four pentanucleotides in the core origin are necessary for T-ag assembly and the induction of structural changes in the core origin. Since all four pentanucleotides in the wild-type origin are necessary for extensive DNA unwinding, we concluded that the second pair of pentanucleotides is required at a step subsequent to the initial assembly process.

scholarly journals Quantifying Soil Compaction in Persimmon Orchards Using ISUM (Improved Stock Unearthing Method) and Core Sampling Methods

Agriculture ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 266 ◽  
Author(s):  
Ehsan Moradi ◽  
Jesús Rodrigo-Comino ◽  
Enric Terol ◽  
Gaspar Mora-Navarro ◽  
Alexandre Marco da Silva ◽  
...  
Keyword(s):  
Ecosystem Services ◽  
Soil Erosion ◽  
Bulk Density ◽  
Soil Compaction ◽  
Structural Changes ◽  
Low Cost ◽  
Positive Contribution ◽  
The Core ◽  
Core Sampling ◽  
Core Method

Agricultural activities induce micro-topographical changes, soil compaction and structural changes due to soil cultivation, which directly affect ecosystem services. However, little is known about how these soil structural changes occur during and after the planting of orchards, and which key factors and processes play a major role in soil compaction due to cultivation works. This study evaluates the improved stock unearthing method (ISUM) as a low-cost and precise alternative to the tedious and costly traditional core sampling method, to characterize the changes in soil compaction in a representative persimmon orchard in Eastern Spain. To achieve this goal, firstly, in the field, undisturbed soil samples using metallic core rings (in January 2016 and 2019) were collected at different soil depths between 45 paired-trees, and topographic variations were determined following the protocol established by ISUM (January 2019). Our results show that soil bulk density (Bd) increases with depth and in the inter-row area, due to the effect of tractor passes and human trampling. The bulk density values of the top surface layers (0–12 cm) showed the lowest soil accumulation, but the highest temporal and spatial variability. Soil consolidation within three years after planting as calculated using the core samples was 12 mm, whereas when calculated with ISUM, it was 14 mm. The quality of the results with ISUM was better than with the traditional core method, due to the higher amount of sampling points. The ISUM is a promising method to measure soil compaction, but it is restricted to the land where soil erosion does not take place, or where soil erosion is measured to establish a balance of soil redistribution. Another positive contribution of ISUM is that it requires 24 h of technician work to acquire the data, whereas the core method requires 272 h. Our research is the first approach to use ISUM to quantify soil compaction and will contribute to applying innovative and low-cost monitoring methods to agricultural land and conserving ecosystem services.

scholarly journals Structural Changes in the Myosin Motors Induced by Stretch and Phosphorylation of the Myosin Regulatory Light Chain in Rat Cardiac Trabeculae

2021 ◽  
Vol 120 (3) ◽  
pp. 251a-252a
Author(s):  
So-Jin Park-Holohan ◽  
Elisabetta Brunello ◽  
Thomas Kampourakis ◽  
Martin Rees ◽  
Malcolm Irving ◽  
...  
Keyword(s):  
Light Chain ◽  
Structural Changes ◽  
Regulatory Light Chain ◽  
Myosin Regulatory Light Chain ◽  
Myosin Motors
Sign in / Sign up

Export Citation Format

Share Document