110 research outputs found
Steps in the bacterial flagellar motor
The bacterial flagellar motor is a highly efficient rotary machine used by
many bacteria to propel themselves. It has recently been shown that at low
speeds its rotation proceeds in steps [Sowa et al. (2005) Nature 437,
916--919]. Here we propose a simple physical model that accounts for this
stepping behavior as a random walk in a tilted corrugated potential that
combines torque and contact forces. We argue that the absolute angular position
of the rotor is crucial for understanding step properties, and show this
hypothesis to be consistent with the available data, in particular the
observation that backward steps are smaller on average than forward steps. Our
model also predicts a sublinear torque-speed relationship at low torque, and a
peak in rotor diffusion as a function of torque
Guillain-Barré syndrome: a century of progress
In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS
3D laser nano-printing on fibre paves the way for super-focusing of multimode laser radiation
Multimode high-power laser diodes suffer from inefficient beam focusing, leading to a focal spot 10–100 times greater than the diffraction limit. This inevitably restricts their wider use in ‘direct-diode’ applications in materials processing and biomedical photonics. We report here a ‘super-focusing’ characteristic for laser diodes, where the exploitation of self-interference of modes enables a significant reduction of the focal spot size. This is achieved by employing a conical microlens fabricated on the tip of a multimode optical fibre using 3D laser nano-printing (also known as multi-photon lithography). When refracted by the conical surface, the modes of the fibre-coupled laser beam self-interfere and form an elongated narrow focus, usually referred to as a ‘needle’ beam. The multiphoton lithography technique allows the realisation of almost any optical element on a fibre tip, thus providing the most suitable interface for free-space applications of multimode fibre-delivered laser beams. In addition, we demonstrate the optical trapping of microscopic objects with a super-focused multimode laser diode beam thus rising new opportunities within the applications sector where lab-on-chip configurations can be exploited. Most importantly, the demonstrated super-focusing approach opens up new avenues for the ‘direct-diode’ applications in material processing and 3D printing, where both high power and tight focusing is required
Phenomenological analysis of ATP dependence of motor protein
In this study, through phenomenological comparison of the velocity-force data
of processive motor proteins, including conventional kinesin, cytoplasmic
dynein and myosin V, we found that, the ratio between motor velocities of two
different ATP concentrations is almost invariant for any substall, superstall
or negative external loads. Therefore, the velocity of motor can be well
approximated by a Michaelis-Menten like formula V=\atp k(F)L/(\atp +K_M),
with the step size, and the external load dependent rate of one
mechanochemical cycle of motor motion in saturated ATP solution. The difference
of Michaelis-Menten constant for substall, superstall and negative
external load indicates, the ATP molecule affinity of motor head for these
three cases are different, though the expression of as a function of
might be unchanged for any external load . Verifications of this
Michaelis-Menten like formula has also been done by fitting to the recent
experimental data
The Origin of Minus-end Directionality and Mechanochemistry of Ncd Motors
Adaptation of molecular structure to the ligand chemistry and interaction with the cytoskeletal filament are key to understanding the mechanochemistry of molecular motors. Despite the striking structural similarity with kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs). Here, by employing a structure-based model of protein folding, we show that a simple repositioning of the neck-helix makes the dynamics of Ncd non-processive and minus-end directed as opposed to kinesin-1. Our computational model shows that Ncd in solution can have both symmetric and asymmetric conformations with disparate ADP binding affinity, also revealing that there is a strong correlation between distortion of motor head and decrease in ADP binding affinity in the asymmetric state. The nucleotide (NT) free-ADP (?-ADP) state bound to MTs favors the symmetric conformation whose coiled-coil stalk points to the plus-end. Upon ATP binding, an enhanced flexibility near the head-neck junction region, which we have identified as the important structural element for directional motility, leads to reorienting the coiled-coil stalk towards the minus-end by stabilizing the asymmetric conformation. The minus-end directionality of the Ncd motor is a remarkable example that demonstrates how motor proteins in the kinesin superfamily diversify their functions by simply rearranging the structural elements peripheral to the catalytic motor head domain
Mechanochemical modeling of dynamic microtubule growth involving sheet-to-tube transition
Microtubule dynamics is largely influenced by nucleotide hydrolysis and the
resultant tubulin configuration changes. The GTP cap model has been proposed to
interpret the stabilizing mechanism of microtubule growth from the view of
hydrolysis effects. Besides, the microtubule growth involves the closure of a
curved sheet at its growing end. The curvature conversion also helps to
stabilize the successive growth, and the curved sheet is referred to as the
conformational cap. However, there still lacks theoretical investigation on the
mechanical-chemical coupling growth process of microtubules. In this paper, we
study the growth mechanisms of microtubules by using a coarse-grained molecular
method. Firstly, the closure process involving a sheet-to-tube transition is
simulated. The results verify the stabilizing effect of the sheet structure,
and the minimum conformational cap length that can stabilize the growth is
demonstrated to be two dimers. Then, we show that the conformational cap can
function independently of the GTP cap, signifying the pivotal role of
mechanical factors. Furthermore, based on our theoretical results, we describe
a Tetris-like growth style of microtubules: the stochastic tubulin assembly is
regulated by energy and harmonized with the seam zipping such that the sheet
keeps a practically constant length during growth.Comment: 23 pages, 7 figures. 2 supporting movies have not been uploaded due
to the file type restriction
Family Firms and Firm Performance: Evidence from Japan
Corrigendum: Nature Structural and Molecular Biology 16 (12), 1331 (2009) doi:10.1038/nsmb1209-1331bInternational audienceThioredoxins (Trxs) are oxidoreductase enzymes, present in all organisms, that catalyze the reduction of disulfide bonds in proteins. By applying a calibrated force to a substrate disulfide, the chemical mechanisms of Trx catalysis can be examined in detail at the single-molecule level. Here we use single-molecule force-clamp spectroscopy to explore the chemical evolution of Trx catalysis by probing the chemistry of eight different Trx enzymes. All Trxs show a characteristic Michaelis-Menten mechanism that is detected when the disulfide bond is stretched at low forces, but at high forces, two different chemical behaviors distinguish bacterial-origin from eukaryotic-origin Trxs. Eukaryotic-origin Trxs reduce disulfide bonds through a single-electron transfer reaction (SET), whereas bacterial-origin Trxs show both nucleophilic substitution (SN2) and SET reactions. A computational analysis of Trx structures identifies the evolution of the binding groove as an important factor controlling the chemistry of Trx catalysis
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