Abstract:
:Kinesin-1 is an ATP-driven molecular motor that transports cellular cargo along microtubules. At low loads, kinesin-1 almost always steps forward, toward microtubule plus ends, but at higher loads, it can also step backward. Backsteps are usually 8 nm but can be larger. These larger backward events of 16 nm, 24 nm, or more are thought to be slips rather than steps because they are too fast to consist of multiple, tightly coupled 8-nm steps. Here, we propose that not only these larger backsteps, but all kinesin-1 backsteps, are slips. We show first that kinesin waits before forward steps for less time than before backsteps and detachments; second, we show that kinesin waits for the same amount of time before backsteps and detachments; and third, we show that by varying the microtubule type, we can change the ratio of backsteps to detachments without affecting forward stepping. Our findings indicate that backsteps and detachments originate from the same state and that this state arises later in the mechanochemical cycle than the state that gives rise to forward steps. To explain our data, we propose that, in each cycle of ATP turnover, forward kinesin steps can only occur before Pi release, whereas backslips and detachments can only occur after Pi release. In the scheme we propose, Pi release gates access to a weak binding K⋅ADP-K⋅ADP state that can slip back along the microtubule, re-engage, release ADP, and try again to take an ATP-driven forward step. We predict that this rescued detachment pathway is key to maintaining kinesin processivity under load.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Toleikis A,Carter NJ,Cross RAdoi
10.1016/j.bpj.2020.09.034subject
Has Abstractpub_date
2020-11-17 00:00:00pages
1984-1994issue
10eissn
0006-3495issn
1542-0086pii
S0006-3495(20)30766-9journal_volume
119pub_type
杂志文章abstract::Translation is a central cellular process and the complexity of its mechanism necessitates mathematical frameworks to better understand system properties and make quantitative predictions. We have developed a gene sequence-specific mechanistic model for translation which accounts for all the elementary steps of transl...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.126128
更新日期:2008-08-01 00:00:00
abstract::Membrane domains known as rafts are rich in cholesterol and sphingolipids, and are thought to be thicker than the surrounding membrane. If so, monolayers should elastically deform so as to avoid exposure of hydrophobic surfaces to water at the raft boundary. We calculated the energy of splay and tilt deformations nece...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.048223
更新日期:2005-02-01 00:00:00
abstract::Three-dimensional structures were determined for three crystal forms of the antigen binding fragment (Fab) of anti-fluorescein antibody 4-4-20 in complex with fluorescein. These included 1) a triclinic (P1) form crystallized in 47% (v/v) 2-methyl-2,4-pentanediol (MPD); 2) a triclinic (P1) form crystallized in 16% (w/v...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(94)80738-6
更新日期:1994-12-01 00:00:00
abstract::Protein splicing is an autocatalytic reaction where an intervening element (intein) is excised and the remaining two flanking sequences (exteins) are joined. The reaction requires specific conserved residues, and activity may be affected by both the intein and the extein sequence. Predicting how sequence will affect a...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.02.037
更新日期:2011-05-04 00:00:00
abstract::The small mechanosensitive channel, MscS, is a part of the turgor-driven solute efflux system that protects bacteria from lysis in the event of osmotic downshift. It has been identified in Escherichia coli as a product of the orphan yggB gene, now called mscS (Levina et al., 1999, EMBO J. 18:1730). Here I show that th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(02)75169-2
更新日期:2002-07-01 00:00:00
abstract::Dendrites of cerebellar Purkinje cells (PCs) respond to brief excitations from parallel fibers with lasting plateau depolarizations. It is unknown whether these plateaus are local events that boost the synaptic signals or they propagate to the soma and directly take part in setting the cell firing dynamics. To address...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.04.056
更新日期:2010-07-21 00:00:00
abstract::High-bandwidth measurements of the ion current through hafnium oxide and silicon nitride nanopores allow the analysis of sub-30 kD protein molecules with unprecedented time resolution and detection efficiency. Measured capture rates suggest that at moderate transmembrane bias values, a substantial fraction of protein ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2013.12.025
更新日期:2014-02-04 00:00:00
abstract::Phase-lifetime spectroscopy was used to measure the kinetics of light-driven proton transients and M intermediate decay of purple membrane. The kinetics were measured in distilled water and in 0.4 M KCl over the pH range of 5.3-8.8. The low ionic strength data showed results that were comparable to previous data. The ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(88)83077-7
更新日期:1988-02-01 00:00:00
abstract::Low frequency audible vibrations are produced by human skeletal muscles undergoing sustained contraction. The effect is easily demonstrable with an electronic stethoscope which amplifies sound below 50 Hz. Autocorrelation analysis of the signal shows that it is periodic with a frequency 25 +/- 2.5 Hz. The quality of t...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(80)85080-6
更新日期:1980-04-01 00:00:00
abstract::Aerotaxis is a particular form of "energy taxis". It is based on a largely elusive signal transduction machinery. In aerotaxis, oxygen dissolved in water plays the role of both attractant (at moderate concentrations) and repellent (at high and low concentrations). Cells swimming from favorable oxygen concentrations in...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74775-4
更新日期:2003-12-01 00:00:00
abstract::The folding pathway of the small α/β protein GB1 has been extensively studied during the past two decades using both theoretical and experimental approaches. These studies provided a consensus view that the protein folds in a two-state manner. Here, we reassessed the folding of GB1, both by experiments and simulations...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2011.09.013
更新日期:2011-10-19 00:00:00
abstract::The [FeFe] hydrogenase from the green alga Chlamydomonas reinhardtii can catalyze the reduction of protons to hydrogen gas using electrons supplied from photosystem I and transferred via ferredoxin. To better understand the association of the hydrogenase and the ferredoxin, we have simulated the process over multiple ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.107.127548
更新日期:2008-10-01 00:00:00
abstract::Nonphotochemical quenching is the protective mechanism against overexcitation of photosystem II, triggered by excess ΔpH in photosynthetic membranes. The light-harvesting complexes (LHCs), the de-epoxidation of violaxanthin to zeaxanthin, and the photosystem II subunit S (PsbS) work in synergy for an optimized multile...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2017.09.034
更新日期:2017-12-05 00:00:00
abstract::This paper describes the use of electrospray ionization-Fourier transform ion cyclotron mass spectrometry (ESI-FTICR-MS) to study the relative stabilities of noncovalent complexes of carbonic anhydrase II (CAII, EC 4.2.1.1) and benzenesulfonamide inhibitors in the gas phase. Sustained off-resonance irradiation collisi...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/s0006-3495(99)77477-1
更新日期:1999-06-01 00:00:00
abstract::Molecular dynamics simulations of protein folding and unfolding are often carried out at temperatures (400-600 K) that are much higher than physiological or room temperature to speed up the (un)folding process. Use of such high temperatures changes both the protein and solvent properties considerably, compared to phys...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(00)76820-2
更新日期:2000-06-01 00:00:00
abstract::Specific proteins and lipids sequester to regions of cell membranes called rafts. Due to their high content of sphingomyelin (SM) and cholesterol, raft bilayers are thicker than nonraft bilayers and, at least at 4 degrees C, are resistant to Triton X-100 extraction. It has been postulated that rafts concentrate protei...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(03)74595-0
更新日期:2003-09-01 00:00:00
abstract::The glucose transporters (GLUT/SLC2A) are members of the major facilitator superfamily. Here, we generated a three-dimensional model for Glut1 using a two-step strategy: 1), GlpT structure as an initial homology template and 2), evolutionary homology using glucose-6-phosphate translocase as a template. The resulting s...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1529/biophysj.104.047886
更新日期:2004-11-01 00:00:00
abstract::We report on a molecular dynamics (MD) simulation of carboxy-myoglobin (MbCO) embedded in a water-trehalose system. The mean square fluctuations of protein atoms, calculated at different temperatures in the 100-300 K range, are compared with those from a previous MD simulation on an H2O-solvated MbCO and with experime...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)76072-9
更新日期:2001-02-01 00:00:00
abstract::Molecular recognition between biotinylated bovine serum albumin and polyclonal, biotin-directed IG antibodies has been measured directly under various buffer conditions using an atomic force microscope (AFM). It was found that even highly structured molecules such as IgG antibodies preserve their specific affinity to ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(96)79814-4
更新日期:1996-05-01 00:00:00
abstract::Enzyme function depends on specific conformational motions. We show that the temperature dependence of enzyme kinetic parameters can provide insight into these functionally relevant motions. While investigating the catalytic properties of IPMDH from Escherichia coli, we found that its catalytic efficiency (k(cat)/K(M,...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2009.04.014
更新日期:2009-06-17 00:00:00
abstract::Probes and biosensors that incorporate luminescent Tb(III) or Eu(III) complexes are promising for cellular imaging because time-gated microscopes can detect their long-lifetime (approximately milliseconds) emission without interference from short-lifetime (approximately nanoseconds) fluorescence background. Moreover, ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2015.06.028
更新日期:2015-07-21 00:00:00
abstract::Chiral objects which scatter and absorb preferentially left versus right circularly polarized light give rise to bright-field circular dichroism (CD) images containing contributions from both these two phenomena. These contributions are separated and characterized mathematically, and the effect of the dimensions of th...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(91)82334-7
更新日期:1991-06-01 00:00:00
abstract::The elastic properties of cylindrical segments of sarcolemma were studied in single striated fibers of the frog semitendinosus muscle. All measurements were made on membranes of retraction zones, cell segments from which the sarcoplasm had retracted. Quantitative morphological studies indicated that three deforming fo...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(70)86312-3
更新日期:1970-05-01 00:00:00
abstract::We analyzed the microstructure in the first-order laser diffraction line from both resting and tetanically contracting single twitch fibers from frog anterior tibial muscle to see if the distribution of sarcomere lengths is continuous or discrete. Measuring the distance between adjacent microstructural elements lying ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(82)84695-X
更新日期:1982-02-01 00:00:00
abstract::The early events in halorhodopsin after light excitation are studied with picosecond time resolution. Absorption and fluorescence measurements show that the electronically excited state of the incorporated retinal has a lifetime of 5 ps. Within that time a red-shifted photoproduct is formed that remains stable for at ...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(85)83876-5
更新日期:1985-01-01 00:00:00
abstract::Autocrine loops formed by growth factors and their receptors have been identified in a large number of developmental, physiological, and pathological contexts. In general, the spatially distributed and recursive nature of autocrine signaling systems makes their experimental analysis, and often even their detection, ve...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/S0006-3495(01)75837-7
更新日期:2001-10-01 00:00:00
abstract::The plasma membrane of cells has a complex architecture based on the bidimensional liquid-crystalline bilayer arrangement of phospho- and sphingolipids, which in turn embeds several proteins and is connected to the cytoskeleton. Several studies highlight the spatial membrane organization into more ordered (Lo or lipid...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2018.11.3141
更新日期:2019-02-05 00:00:00
abstract::Numerous membrane-transport proteins are major drug targets, and therefore a key ingredient in pharmaceutical development is the availability of reliable, efficient tools for membrane transport characterization and inhibition. Here, we present the use of evanescent-wave sensing for screening of membrane-protein-mediat...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2010.03.059
更新日期:2010-07-07 00:00:00
abstract::Based on differences between the x-ray crystal structures of ligand-bound and unbound forms, the activation of the erythropoietin receptor (EPOR) was initially proposed to involve a cross-action scissorlike motion. However, the validity of the motions involved in the scissorlike model has been recently challenged. Her...
journal_title:Biophysical journal
pub_type: 杂志文章
doi:10.1016/j.bpj.2016.12.042
更新日期:2017-02-28 00:00:00
abstract::Single molecule force spectroscopy methods, such as optical and magnetic tweezers and atomic force microscopy, have opened up the possibility to study biological processes regulated by force, dynamics of structural conformations of proteins and nucleic acids, and load-dependent kinetics of molecular interactions. Amon...
journal_title:Biophysical journal
pub_type: 杂志文章,评审
doi:10.1016/j.bpj.2013.08.007
更新日期:2013-09-17 00:00:00