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Masaki Sasai

Publications and source records attributed to Masaki Sasai.

12 recordsLinked to original sources
PubMed2026

Cohesin prevents local mixing of condensed euchromatic domains in living human cells.

The human genome is folded into chromatin loops by the cohesin complex, forming functional chromatin domains that underlie transcription and DNA replication/repair. However, how cohesin organizes these domains in living cells, especially in active euchromatin, remains elusive. Here, to address this question, we combined single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy with euchromatin-specific labeling of histone variant H3.3. Using this nanoscopic approach, we revealed that euchromatin forms condensed domains that are constrained by cohesin-mediated loops. This organization refines the classical view of euchromatin as largely open, in line with emerging evidence. Transcription machinery appears to be located near the condensed domain surfaces/borders. Cohesin loss increased nucleosome-level fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings suggest a physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.

Humans↗
PubMed2006

Modulation of the reaction rate of regulating protein induces large morphological and motional change of amoebic cell.

Morphologies of moving amoebae are categorized into two types. One is the "neutrophil" type in which the long axis of cell roughly coincides with its moving direction. This type of cell extends a leading edge at the front and retracts a narrow tail at the rear, whose shape has been often drawn as a typical amoeba in textbooks. The other one is the "keratocyte" type with widespread lamellipodia along the front side arc. Short axis of cell in this type roughly coincides with its moving direction. In order to understand what kind of molecular feature causes conversion between two types of morphologies, and how two typical morphologies are maintained, a mathematical model of amoebic cells is developed. This model describes movement of cell and intracellular reactions of activator, inhibitor and actin filaments in a unified way. It is found that the producing rate of activator is a key factor of conversion between two types. This model also explains the observed data that the keratocyte type cells tend to rapidly move along a straight line. The neutrophil type cells move along a straight line when the moving velocity is small, but they show fluctuated motions deviating from a line when they move as fast as the keratocyte type cells. Efficient energy consumption in the neutrophil type cells is predicted.

Amoeba↗
PubMed2006

Flexibly varying folding mechanism of a nearly symmetrical protein: B domain of protein A.

The folding pathway of the B domain of protein A is the pathway most intensively studied by computer simulations. Recent systematic measurement of Phi values by Sato et al., however, has shown that none of the published computational predictions is consistent with the detailed features of the experimentally observed folding mechanism. In this article we use a statistical mechanical model of folding to show that sensitive dependence of multiple transition state ensembles on temperature and the denaturant concentration is the key to resolving the inconsistency among simulations and the experiment. Such sensitivity in multiple transition state ensembles is a natural consequence of symmetry-breaking in a nearly symmetrical protein.

Dimerization↗
PubMed2005

Correlation between evolutionary structural development and protein folding.

Evolution should have played important roles in determining folding mechanisms and structures of proteins. In this article we discuss how the folding mechanisms had been affected by the early stage of evolution through which the uniqueness of structure had developed. Although the process of such early-time evolution has remained a mystery, a plausible scenario is that the evolution of proteins toward the ordered structures was guided by functional selection pressure as demonstrated in vitro and in silico. We examine the in silico functional selection of sequences and show that there is a significant correlation between two different processes toward the unique 3D structure, the evolutionary development of structure through sequence selection, and the folding process of the resultant sequence. This finding could be rephrased as protein folding recapitulates the emergence of topology in the molecular evolution. The correlation suggests a guideline for engineering foldable proteins.

Binding Sites↗
PubMed2005

Fluctuating hydration structure around nanometer-size hydrophobic solutes. I. Caging and drying around C60 and C60H60 spheres.

The hydration structure around nanometer-size hydrophobic solutes is studied with molecular dynamics simulation by taking aqueous solutions of C60 and C60H60 as examples. In the hydration shell around a single C60 or C60H60, dipoles of simulated water molecules tend to be aligned to form the vortexlike coherent pattern which lasts for 100 ps, while individual water molecules stay within the hydration shell for about 10 ps. This structural pattern organized by fluctuating and diffusively moving molecules should be called a "fluctuating cage". In the narrow region between a pair of C60 molecules or a pair of C60H60 molecules, water density strongly fluctuates and is correlated to the mean force between solutes. The fluctuating caging and drying between solutes affect the hydrophobic interaction and dynamical behaviors of solutes.

Fullerenes↗
PubMed2005

Inertia of amoebic cell locomotion as an emergent collective property of the cellular dynamics.

Amoebic cells are ubiquitous in many species and have been used as model systems to study the eukaryotic cellular locomotion. We construct a model of amoebic cells on two-dimensional grids, which describes sensing, cell status, and locomotion in a unified way. We show that the averaged position of simulated cells is described by a second-order differential equation of motion and that the mechanical pushing at the initial moment boosts the cell movement, which continues after the cell is released from the pushing. These "inertialike" features suggest the possibility of Newtonian-type motions in chemical distributions of the signaling molecule. We show, as an example, the possibility of rotating motion in a "centripetal" distribution. The observed inertial motion is an emergent collective dynamics, which is controlled by diffusive and chemical processes in the cell.

Amoeba↗
PubMed2004

Self-consistent proteomic field theory of stochastic gene switches.

We present a self-consistent field approximation approach to the problem of the genetic switch composed of two mutually repressing/activating genes. The protein and DNA state dynamics are treated stochastically and on an equal footing. In this approach the mean influence of the proteomic cloud created by one gene on the action of another is self-consistently computed. Within this approximation a broad range of stochastic genetic switches may be solved exactly in terms of finding the probability distribution and its moments. A much larger class of problems, such as genetic networks and cascades, also remain exactly solvable with this approximation. We discuss, in depth, certain specific types of basic switches used by biological systems and compare their behavior to the expectation for a deterministic switch.

Animals↗
PubMed2004

Dynamical transition and proteinquake in photoactive yellow protein.

Conformational dynamics in protein functioning covers a wide range of time scales from nanosecond fluctuations around a conformation to the large-amplitude conformational changes of milliseconds or longer. We illustrate a picture of cooperative coupling among such motions of different time scales in a model protein, photoactive yellow protein, by proposing a model that can consistently explain the experimental results on the photocycle of photoactive yellow protein. The model provides a scenario in which the global collective motion induced by the unfolding of the N-terminal domain promotes the loosening of the atomistic packing around the chromophore, which produces the favorable molecular environment for the photoexcited chromophore, thereby stabilizing the partially unfolded intermediate in the photocycle. The proteinquake, the large conformational change triggered by the local structural disturbance, plays a decisive role in controlling the kinetics of functioning.

Bacterial Proteins↗
PubMed2004

Squeezed exponential kinetics to describe a nonglassy downhill folding as observed in a lattice protein model.

We previously studied the so-called strange kinetics in the two-dimensional lattice HP model. To further study the strange kinetics, folding processes of a 27-mer cubic lattice protein model with Gō potential were investigated by simulating how the bundle of folding trajectories, consisting of a number of independent Monte Carlo simulations, evolves as the folding reaction proceeds, covering a wide range of temperature. Three realms of folding kinetics were observed depending on temperature. Although at temperatures where folding was two-state-like, the kinetics was conventional single exponential, we found that the time course data were well represented by a squeezed (or "shrunken") exponential function, exp [-(t/tau)beta] with beta > 1, at temperatures lower than the folding temperature, where folding was fastest and of a nonglassy downhill type. The squeezed exponential kinetics was found to pertain to the subdiffusion on the nonglassy downhill free energy surface and presents a marked contrast both to the single exponential kinetics and to the stretched exponential kinetics that was observed at lower temperatures where folding was also downhill but topological frustration came into effect. The observed temperature dependence of the folding kinetics suggests that some small single-domain proteins may follow the squeezed exponential kinetics at about the room temperature.

Kinetics↗
PubMed2003

Stochastic gene expression as a many-body problem.

Gene expression has a stochastic component because of the single-molecule nature of the gene and the small number of copies of individual DNA-binding proteins in the cell. We show how the statistics of such systems can be mapped onto quantum many-body problems. The dynamics of a single gene switch resembles the spin-boson model of a two-site polaron or an electron transfer reaction. Networks of switches can be approximately described as quantum spin systems by using an appropriate variational principle. In this way, the concept of frustration for magnetic systems can be taken over into gene networks. The landscape of stable attractors depends on the degree and style of frustration, much as for neural networks. We show the number of attractors, which may represent cell types, is much smaller for appropriately designed weakly frustrated stochastic networks than for randomly connected networks.

Algorithms↗
PubMed2002

Conformational change of the actomyosin complex drives the multiple stepping movement.

Actin-myosin (actomyosin) generates mechanical force by consuming ATP molecules. We apply the energy landscape perspective to address a controversial issue as to whether the myosin head moves with multiple steps after a single ATP hydrolysis or only a single mechanical event of the lever-arm swinging follows a single ATP hydrolysis. Here we propose a theoretical model in which the refolding of the partially unfolded actomyosin complex and the movement of the myosin head along the actin filament are coupled. A single ATP hydrolysis is followed by the formation of a high free-energy partially unfolded actomyosin complex, which then gradually refolds with a concomitant multiple stepping movement on the way to the lowest free-energy rigor state. The model quantitatively explains the single-molecular observation of the multiple stepping movement and is consistent with structural observations of the disorder in the actomyosin-binding process. The model also explains the observed variety in dwell time before each step, which is not accounted for by previous models, such as the lever-arm or ratchet models.

Actins↗