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Chen et al. solved the crystal structure of bovine DHX36 bound to a DNA with a G-quadruplex (G4) and a single-stranded DNA segment. They believed that the mechanism they proposed may represent a general model for describing how a G4-unfolding helicase recognizes and unfolds G4 DNA. Their conclusion is interesting, however, we noticed that their linear DNA substrate (DNAMyc) that harbors a Myc-promoter-derived G4-forming sequence was directly used without pre-folding. This raises the question whether the structure they obtained really reflects DHX36-mediated G4 recognition and unfolding, or just only represents a DHX36-binding-induced quasi-folded G4 structure. By a combination of polymerase extension, DMS footprinting, stopped-flow, and smFRET assays, we obtained clear evidences that do not support their ATP-independent one-base translocation structural model. We further revealed that the oscillation of FRET signal they observed should correspond to a repetitive G4 binding, but not unfolding, by DHX36.

A model for the unidirectional movement of dynein is presented based on structural observations and biochemical experimental results available. In this model, the binding affinity of dynein for microtubule is independent of its nucleotide state and the change between strong and weak microtubule-binding is determined naturally by the variation of relative orientation between the stalk and microtubule as the stalk rotates following nucleotide-state transition. Thus the enigmatic communication from the ATP binding site in the globular domain to the far MT-binding site in the tip of the stalk, which is prerequisite in conventional models, is not required. Using the present model, the previous experimental results such as the effect of ATP and ADP bindings on dissociation of dynein from microtubule, the processive movement of single-headed axonemal dyneins at saturating ATP concentration, the load dependence of step size for the processive movement of two-headed cytoplasmic dyneins and the dependence of stall force on ATP concentration can be well explained.

Mouse prion protein PrP106-126 is a peptide corresponding to the residues 107-127 of human prion protein. It has been shown that PrP106-126 can reproduce the main neuropathological features of prionrelated transmissible spongiform encephalopathies and can form amyloid-like fibrils in vitro. The conformational characteristics of PrP106-126 fibril have been investigated by electron microscopy, CD spectroscopy, NMR and molecular dynamics simulations. Recent researches have found out that PrP106-126 in water assumes a stable structure consisting of two parallel beta-sheets that are tightly packed against each other. In this work we perform molecular dynamics simulation to reveal the elongation mechanism of PrP106-126 fibril. Influenced by the edge strands of the fibril which already adopt beta-sheets conformation, single PrP106-126 peptide forms beta-structure and becomes a new element of the fibril. Under acidic condition, single PrP106-126 peptide adopts a much larger variety of conformations than it does under neural condition, which makes a peptide easier to be influenced by the edge strands of the fibril. However, acidic condition dose not largely affect the stability of PrP106-126 peptide fibril. Thus, the speed of fibril elongation can be dramatically increased by lowering the pH value of the solution. The pH value was adjusted by either changing the protonation state of the residues or adding hydronium ions (acidic solution) or hydroxyl ions (alkaline solution). The differences between these two approaches are analyzed here., Comment: 16 pages, 14 figures

In eukaryote nucleosome, DNA wraps around a histone octamer in a left-handed way. We study the process of chirality formation of nucleosome with Brownian dynamics simulation. We model the histone octamer with a quantitatively adjustable chirality: left-handed, right-handed or non-chiral, and simulate the dynamical wrapping process of a DNA molecule on it. We find that the chirality of a nucleosome formed is strongly dependent on that of the histone octamer, and different chiralities of the histone octamer induce its different rotation directions in the wrapping process of DNA. In addition, a very weak chirality of the histone octamer is quite enough for sustaining the correct chirality of the nucleosome formed. We also show that the chirality of a nucleosome may be broken at elevated temperature., Comment: 12 pages, 8 figues

The effects of monovalent (Na+, K+) and divalent (Mg2+, Ca2+, Mn2+) ions on the interaction between DNA and histone are studied using the molecular combing technique. Lamda-DNA molecules and DNA-histone complexes incubated with metal cations (Na+, K+, Mg2+, Ca2+, Mn2+) are stretched on hydrophobic surfaces, and directly observed by fluorescence microscopy. The results indicate that when these cations are added into the DNA solution, the fluorescence intensities of the stained DNA are reduced differently. The monovalent cations (Na+, K+) inhibit binding of histone to DNA. The divalent cations (Mg2+, Ca2+, Mn2+) enhance significantly the binding of histone to DNA and the binding of the DNA-histone complex to the hydrophobic surface. Mn2+ also induces condensation and aggregation of the DNA-histone complex., Comment: 11 pages, 7 figures

A model for the processive movement of dynein is presented based on experimental observations available. In the model, the change from strong microtubule-binding to weak binding of dynein is determined naturally by the variation of the relative orientation between the two interacting surfaces of the stalk tip and the microtubule as the stalk rotates from the ADP.Vi-state orientation to the apo-state orientation. This means that the puzzling communication from the ATP binding site in the globular head to the MT-binding site in the tip of the stalk, which is prerequisite in the conventional model, is not required. Using the present model, the previous experimental results, such as (i) the step size of a dynein being an integer times of the period of the MT lattice, (ii) the dependence of the step size on load, i.e., the step size decreasing with the increase of load, and (iii) the stall force being proportional to [ATP] at low [ATP] and becoming saturated at high [ATP], are well explained., Comment: 16 pages, 5 figures

Using the model for the processive movement of a dimeric kinesin we proposed before, we study the dynamics of a number of mutant homodimeric and heterodimeric kinesins that were constructed by Kaseda et al. (Kaseda, K., Higuchi, H. and Hirose, K. PNAS 99, 16058 (2002)). The theoretical results of ATPase rate per head, moving velocity, and stall force of the motors show good agreement with the experimental results by Kaseda et al.: The puzzling dynamic behaviors of heterodimeric kinesin that consists of two distinct heads compared with its parent homodimers can be easily explained by using independent ATPase rates of the two heads in our model. We also study the collective kinetic behaviors of kinesins in MT-gliding motility. The results explains well that the average MT-gliding velocity is independent of the number of bound motors and is equal to the moving velocity of a single kinesin relative to MT., Comment: 18 pages, 5 figures

Myosin V and myosin VI are two classes of two-headed molecular motors of the myosin superfamily that move processively along helical actin filaments in opposite directions. Here we present a hand-over-hand model for their processive movements. In the model, the moving direction of a dimeric molecular motor is automatically determined by the relative orientation between its two heads at free state and its head's binding orientation on track filament. This determines that myosin V moves toward the barbed end and myosin VI moves toward the pointed end of actin. During the moving period in one step, one head remains bound to actin for myosin V whereas two heads are detached for myosin VI: The moving manner is determined by the length of neck domain. This naturally explains the similar dynamic behaviors but opposite moving directions of myosin VI and mutant myosin V (the neck of which is truncated to only one-sixth of the native length). Because of different moving manners, myosin VI and mutant myosin V exhibit significantly broader step-size distribution than native myosin V. However, all three motors give the same mean step size of 36 nm (the pseudo-repeat of actin helix). Using the model we study the dynamics of myosin V quantitatively, with theoretical results in agreement with previous experimental ones., Comment: 18 pages, 7 figures

Kinesin motors have been studied extensively both experimentally and theoretically. However, the microscopic mechanism of the processive movement of kinesin is still an open question. In this paper, we propose a hand-over-hand model for the processivity of kinesin, which is based on chemical, mechanical, and electrical couplings. In the model the processive movement does not need to rely on the two heads' coordination in their ATP hydrolysis and mechanical cycles. Rather, the ATP hydrolyses at the two heads are independent. The much higher ATPase rate at the trailing head than the leading head makes the motor walk processively in a natural way, with one ATP being hydrolyzed per step. The model is consistent with the structural study of kinesin and the measured pathway of the kinesin ATPase. Using the model the estimated driving force of ~ 5.8 pN is in agreements with the experimental results (5~7.5 pN). The prediction of the moving time in one step (~10 microseconds) is also consistent with the measured values of 0~50 microseconds. The previous observation of substeps within the 8-nm step is explained. The shapes of velocity-load (both positive and negative) curves show resemblance to previous experimental results., Comment: 22 pages, 6 figures

We propose a two-dimensional model for a complete description of the dynamics of molecular motors, including both the processive movement along track filaments and the dissociation from the filaments. The theoretical results on the distributions of the run length and dwell time at a given ATP concentration, the dependences of mean run length, mean dwell time and mean velocity on ATP concentration and load are in good agreement with the previous experimental results., Comment: 10 pages, 7 figures

Molecular combing is a powerful and simple method for aligning DNA molecules onto a surface. Using this technique combined with fluorescence microscopy, we observed that the length of lambda-DNA molecules was extended to about 1.6 times their contour length (unextended length, 16.2 micrometers) by the combing method on hydrophobic polymethylmetacrylate (PMMA) coated surfaces. The effects of sodium and magnesium ions and pH of the DNA solution were investigated. Interestingly, we observed force-induced melting of single DNA molecules., Comment: 12 pages

Using a Brownian dynamics simulation, we numerically studied the interaction of DNA with histone and proposed an octamer-rotation model to describe the process of nucleosome formation. Nucleosome disruption under stretching was also simulated. The theoretical curves of extension versus time as well as of force versus extension are consistent with previous experimental results., Comment: 16 pages, 11 figures