599 research outputs found
Mechanism of unidirectional movement of kinesin motors
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 figure
Model for processive movement of myosin V and myosin VI
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 figure
LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma
Objectives: To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC).
Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R “clusterProfiler” package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins.
Results: LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins.
Conclusion: LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction
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