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921.
922.
923.
A structural change in the kinesin motor protein that drives motility 总被引:34,自引:0,他引:34
Rice S Lin AW Safer D Hart CL Naber N Carragher BO Cain SM Pechatnikova E Wilson-Kubalek EM Whittaker M Pate E Cooke R Taylor EW Milligan RA Vale RD 《Nature》1999,402(6763):778-784
Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer. 相似文献
924.
925.
926.
Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein. The normal CAG repeat range is 5-36, whereas 38 or more repeats are found in the diseased state; the severity of disease is roughly proportional to the number of CAG repeats. HD shows anticipation, in which subsequent generations display earlier disease onsets due to intergenerational repeat expansion. For longer repeat lengths, somatic instability of the repeat size has been observed both in human cases at autopsy and in transgenic mouse models containing either a genomic fragment of human HD exon 1 (ref. 9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10). With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation, suggesting important functional correlations between repeat length and pathology. Because dinucleotide repeat instability is known to increase when the mismatch repair enzyme MSH2 is missing, we examined instability of the HD CAG repeat by crossing transgenic mice carrying exon 1 of human HD (ref. 16) with Msh2-/- mice. Our results show that Msh2 is required for somatic instability of the CAG repeat. 相似文献
927.
928.
Bacterial suicide through stress 总被引:9,自引:0,他引:9
Outside of the laboratory, bacterial cells are constantly exposed to stressful conditions, and an ability to resist those
stresses is essential to their survival. However, the degree of stress required to bring about cell death varies with growth
phase, amongst other parameters. Exponential phase cells are significantly more sensitive to stress than stationary phase
ones, and a novel hypothesis has recently been advanced to explain this difference in sensitivity, the suicide response. Essentially,
the suicide response predicts that rapidly growing and respiring bacterial cells will suffer growth arrest when subjected
to relatively mild stresses, but their metabolism will continue: a burst of free-radical production results from this uncoupling
of growth from metabolism, and it is this free-radical burst that is lethal to the cells, rather than the stress per se. The
suicide response hypothesis unifies a variety of previously unrelated empirical observations, for instance induction of superoxide
dismutase by heat shock, alkyl-hydroperoxide reductase by osmotic shock and catalase by ethanol shock. The suicide response
also has major implications for current [food] processing methods.
Received 29 March 1999; received after revision 14 May 1999; accepted 17 May 1999 相似文献
929.
At the end of mitosis, daughter cells are separated from each other by cytokinesis. This process involves equal partitioning
and segregation of cytoplasm between the two cells. Despite years of study, the mechanism driving cytokinesis in animal cells
is not fully understood. Actin and myosin are major components of the contractile ring, the structure at the equator between
the dividing cells that provides the force necessary to constrict the cytoplasm. Despite this, there are also tantalizing
results suggesting that cytokinesis can occur in the absence of myosin. It is unclear what the roles are of the few other
contractile ring components identified to date. While it has been difficult to identify important proteins involved in cytokinesis,
it has been even more challenging to pinpoint the regulatory mechanisms that govern this vital process. Cytokinesis must be
precisely controlled both spatially and temporally; potential regulators of these parameters are just beginning to be identified.
This review discusses the recent progress in our understanding of cytokinesis in animal cells and the mechanisms that may
regulate it.
Received 24 August 1998; received after revision 9 October 1998; accepted 9 October 1998 相似文献
930.
Images, calculated from electron micrographs, show the three-dimensional structures of microtubules and tubulin sheets decorated stoichiometrically with motor protein molecules. Dimeric motor domains (heads) of kinesin and ncd, the kinesin-related protein that moves in the reverse direction, each appeared to bind to tubulin in the same way, by one of their two heads. The second heads show an interesting difference in position that seems to be related to the directions of movement of the two motors. X-ray crystallographic results showing the structures of kinesin and ncd to be very similar at atomic resolution, and homologous also to myosin, suggest that the two motor families may use mechanisms that have much in common. Nevertheless, myosins and kinesins differ kinetically. Also, whereas conformational changes in the myosin catalytic domain are amplified by a long lever arm that connects it to the stalk domain, kinesin and ncd do not appear to possess a structure with a similar function but may rely on biased diffusion in order to move along microtubules. 相似文献