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The Free Energy Profile of Tubulin Straight-Bent Conformational Changes, with Implications for Microtubule Assembly and Drug Discovery

Lili X. Peng, Monica T. Hsu, Massimiliano Bonomi, David A. Agard, Matthew P. Jacobson, Mark S. Alber
2014 PLoS Computational Biology  
ab-tubulin dimers need to convert between a 'bent' conformation observed for free dimers in solution and a 'straight' conformation required for incorporation into the microtubule lattice.  ...  Here, we investigate the free energy landscape of abtubulin using molecular dynamics simulations, emphasizing implications for models of assembly, and modulation of the conformational landscape by colchicine  ...  Acknowledgments Supercomputing resources from NSF XSEDE (at the Texas Advanced Computer Center) and the UCSF QB3 cluster were used for the simulations.  ... 
doi:10.1371/journal.pcbi.1003464 pmid:24516374 pmcid:PMC3916224 fatcat:febhs45qsrflbnuliesq2e76ve

Multi-scale Computational Modeling of Tubulin-Tubulin Lateral Interaction [article]

Mahya Hemmat, Brian T Castle, Jonathan N Sachs, David J Odde
2019 bioRxiv   pre-print
We found that the lateral free energy is not significantly different among three nucleotide states of tubulin, GTP, GDP, and GMPCPP, and is estimated to be ≅-11 kBT.  ...  bond is required for microtubule assembly.  ...  This study was supported by National Institutes of Health under award number R01-AG053951 and the Institute for Engineering in Medicine (IEM) award at the University of Minnesota to DJO.  ... 
doi:10.1101/624213 fatcat:f7fkp3plxjct7maql5ongi3zym

Drugs that target dynamic microtubules: A new molecular perspective

Richard A. Stanton, Kim M. Gernert, James H. Nettles, Ritu Aneja
2011 Medicinal research reviews (Print)  
In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function  ...  relative to the molecular vectors of microtubule assembly or disassembly.  ...  This can be attributed to the conformational change in paxlitaxel-bound tubulin that maintains a straight biological vector in the dimer, which aligns with the biological vector of the growing microtubule  ... 
doi:10.1002/med.20242 pmid:21381049 pmcid:PMC3155728 fatcat:d3nertldnbfiferunup34dz2u4

Structural basis of human kinesin-8 function and inhibition

Julia Locke, Agnel Praveen Joseph, Alejandro Peña, Martin M. Möckel, Thomas U. Mayer, Maya Topf, Carolyn A. Moores
2017 Proceedings of the National Academy of Sciences of the United States of America  
The Kif18A motor domain drives ATP-dependent plus-end microtubule gliding, and undergoes conformational changes consistent with canonical mechanisms of plus-end-directed motility.  ...  Kinesin motors play diverse roles in mitosis and are targets for antimitotic drugs.  ...  We thank Anthony Roberts for help in designing the TIRF assays, access to the TIRF microscope, and very useful discussions.  ... 
doi:10.1073/pnas.1712169114 pmid:29078367 pmcid:PMC5692573 fatcat:geex4o2ginh6ldbldiiwawxxae

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

C. Appert-Rolland, M. Ebbinghaus, L. Santen
2015 Physics reports  
The cytoskeleton, composed of three types of filaments, determines the shape of the cell and plays a role in cell motion. It also serves as a road network for the so-called cytoskeletal motors.  ...  After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the transportation of large cargos by multiple motors, we concentrate on axonal  ...  We also thank Daniel Bahr for his help, in particular for some of the figures.  ... 
doi:10.1016/j.physrep.2015.07.001 fatcat:7rzhjd7ouvcujcbv57po42xtxi

1 Keynote address by Nobel Laureate Phillip A. Sharp the 21st century opened with a revolution in RNA biology

Phillip A. Sharp
2015 Journal of Biomolecular Structure and Dynamics  
The discoveries of RNA interference and the evolutionary conservation of microRNAs at the turn of the century heralded a revolution in RNA Biology and the development of important innovations.  ...  Excitingly, these insights and others are now being translated into new treatments for diseases and control of plant pathogens. 2 His Nobel Lecture and his speculative commentary on "What does the Future  ...  DNA sequences that interfere with transcription: Implications for genome function and stability. Chemical Reviews, 113, 8620-8637. Belotserkovskii Authors thank TATA-OSDD, J. C.  ... 
doi:10.1080/07391102.2015.1032624 fatcat:w7iil7k3ize77bjkthcyi52ohy

Ultrastructural Modelling of the Matrix-Cilium-Golgi Continuum in Hyaline Chondrocytes

Michael John Jennings
2015 Zenodo  
The extracellular matrix was found to consist of interconnected tethered proteoglycans and matrix granules, with the granules composed of aggregates of finer components.  ...  Overlooked for decades as an evolutionary vestigial organelle, the primary cilium has recently become the focus of intensive investigations into understanding of the physical structure and processes of  ...  Particle attachment to membranes is responsible for membrane deformation, and results in changes to the elastic energy of the membrane [1075] .  ... 
doi:10.5281/zenodo.4632565 fatcat:vyr7wbzun5fjxm4tu3r7n64vgi


2018 Seibutsu Butsuri  
Biophysical Society of Japan (BSJ) grants "Early Career Award in Biophysics" and "Early Career Presentation Award" to young BSJ members for their excellent presentations that show great potential to contribute  ...  Up to five awardees of the Early Career Award in Biophysics will be selected and announced at the banquet 3SEA-5 光遺伝子操作による単一の糸球体の活性により誘因される恐怖行動の探索 Immobility responses are induced by photoactivation of  ...  The microtubule cytoskeleton is formed by assembling the heterodimer consisting of α-tubulin (αTUB) and β-tubulin (βTUB).  ... 
doi:10.2142/biophys.58.s1 fatcat:6slkwnu64fen7cjixehxrcmdzm

Filming Biomolecular Processes by High-Speed Atomic Force Microscopy

Toshio Ando, Takayuki Uchihashi, Simon Scheuring
2014 Chemical Reviews  
In the other cases, native membranes are placed and SLBs are formed on bare mica surfaces. Streptavidin 2D crystals are formed on biotincontaining SLBs.  ...  Biographies 3181 Acknowledgments 3182 Abbreviations 3182 References 3183 a Native membranes and live cells are placed on chemically modified mica surfaces. b Native membranes are suspended over nanowells  ...  ACKNOWLEDGMENTS We thank colleagues of our laboratories and collaborators for their enthusiasm to pioneer biological research by the development and use of HS-AFM techniques. HS-AFM research in the  ... 
doi:10.1021/cr4003837 pmid:24476364 pmcid:PMC4076042 fatcat:sklo6box3nhazblvdlz4tlcl5a

Half a century of amyloids: past, present and future

Pu Chun Ke, Ruhong Zhou, Louise C Serpell, Roland Riek, Tuomas P J Knowles, Hilal A Lashuel, Ehud Gazit, Ian W Hamley, Thomas P Davis, Marcus Fändrich, Daniel Erik Otzen, Matthew R Chapman (+3 others)
2020 Chemical Society Reviews  
Amyloid diseases are global epidemics with profound health, social and economic implications and yet remain without a cure.  ...  This dire situation calls for research into the origin and pathological manifestations of amyloidosis to stimulate continued development of new therapeutics.  ...  We thank Aparna Nandakumar, Aleksandr Kakinen and Kairi Koppel for their assistance with the manuscript preparation.  ... 
doi:10.1039/c9cs00199a pmid:32632432 pmcid:PMC7445747 fatcat:m6hkfmvnvrhxxiluxelwxfxxim

Thirty-seventh Annual Meeting February 14-18, 1993 Washington Convention Center Washington, D.C. Wednesday Symposia and Posters, Part III

1993 Biophysical Journal  
To determine changes in CBF and [Ca2+]i of the same cell, tracheal epithelial cells were obtained from sheep by dissociation with protease and grown in culture for 2-14 days.  ...  attributed to the activation energy for the dissociation process (80 ± 20 keal/mol of duplex).  ...  free-energy changes in the latter.  ... 
doi:10.1016/s0006-3495(93)81410-3 fatcat:wwy72envojaprjz5fgeuktvxte

Emergent complexity of the cytoskeleton: from single filaments to tissue

F. Huber, J. Schnauß, S. Rönicke, P. Rauch, K. Müller, C. Fütterer, J. Käs
2013 Advances in Physics  
or self-assembly.  ...  Nevertheless (and despite the field's relative novelty), the physics approach has already proved to be extremely successful in revealing very fundamental concepts of cytoskeleton organization and behavior  ...  This work was supported by the graduate school "Building with Molecules and Nano-Objects" (BuildMoNa).  ... 
doi:10.1080/00018732.2013.771509 pmid:24748680 pmcid:PMC3985726 fatcat:s4cepfaqgfhexhoamp73toygsa

Advances in Hydrogen Exchange Mass Spectrometry to Study Microtubules and MAPs [article]

Kyle Burns, University Of Calgary, University Of Calgary, David Schriemer
The regulation of microtubule dynamics is accomplished by microtubule associated proteins that can interact with microtubules, or its tubulin dimer, to induce polymerization or depolymerization.  ...  Microtubules are a fundamental component to the cellular cytoskeleton and are responsible for cell structure, motility, intracellular transport, and formation of the mitotic spindle.  ...  motor and the bent -tubulin state.  ... 
doi:10.11575/prism/24725 fatcat:wf6ak5pgvzbavettyvxmg7kcbm

Chemomechanical simulation of microtubule dynamics

Matthias Schmidt, Technische Universität Dortmund
In addition to analyzing different properties of the simulated microtubules and investigating the effects of dilution, i.e., the sudden decrease of the concentration of free tubulin dimers around the microtubule  ...  These chemical processes are the polymerization and depolymerization of tubulin dimers, the building blocks of microtubules, the formation and rupture of lateral bonds between neighboring tubulin monomers  ...  Carsten Lindner and Lina Heydenreich for proofreading parts of the manuscript. Lastly, I want to thank my office colleagues for discussions on-and off-topic of this thesis.  ... 
doi:10.17877/de290r-22030 fatcat:ipqsnpt4pbbkxkfr6ixp2cz4se

Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting

Elisabeth Wik, Jone Trovik, Ole E. Iversen, Ingeborg B. Engelsen, Ingunn M. Stefansson, Liv C. Vestrheim, Hans K. Haugland, Lars A. Akslen, Helga B. Salvesen
2009 American Journal of Obstetrics and Gynecology  
The overall goal for the scientific activity is to explore potential biomarkers to improve and individualize treatment for women with gynecologic cancer.  ...  systematic collection for a biobank from gynecologic malignancies, at the Department of Obstetrics and Gynecology, Haukeland University Hospital was initiated in 2001.  ...  of elongation and shortening. 152 Stathmin is demonstrated to destabilize microtubules potentially through two different routes: By preventing the assembly of tubulin and by stimulation of the microtubule  ... 
doi:10.1016/j.ajog.2009.07.029 pmid:19800606 fatcat:sfbo2g2v2fa6biwwkoixznmj2q
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