نتایج جستجو برای: inactive dynamics

تعداد نتایج: 468961  

2010
Shakil M. Khan Yves Lespérance

Most previous logical accounts of goals do not deal with prioritized goals and goal dynamics properly. Many are restricted to achievement goals. In this paper, we develop a logical account of goal change that addresses these deficiencies. In our account, we do not drop lower priority goals permanently when they become inconsistent with other goals and the agent’s knowledge; rather, we make such...

Journal: :Cell 2015
Aashish Manglik Tae Hun Kim Matthieu Masureel Christian Altenbach Zhongyu Yang Daniel Hilger Michael T. Lerch Tong Sun Kobilka Foon Sun Thian Wayne L. Hubbell R. Scott Prosser Brian K. Kobilka

G-protein-coupled receptors (GPCRs) transduce signals from the extracellular environment to intracellular proteins. To gain structural insight into the regulation of receptor cytoplasmic conformations by extracellular ligands during signaling, we examine the structural dynamics of the cytoplasmic domain of the β2-adrenergic receptor (β2AR) using (19)F-fluorine NMR and double electron-electron r...

Journal: :Cell 2013
Anton Arkhipov Yibing Shan Rahul Das Nicholas F. Endres Michael P. Eastwood David E. Wemmer John Kuriyan David E. Shaw

Dimerization-driven activation of the intracellular kinase domains of the epidermal growth factor receptor (EGFR) upon extracellular ligand binding is crucial to cellular pathways regulating proliferation, migration, and differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting that the mechanism regulating EGFR activity may be subtle. The membrane itself may play a role ...

2017
Kristine Østevold Ana V. Meléndez Friederike Lehmann Gudula Schmidt Klaus Aktories Carsten Schwan

Microtentacles are mostly microtubule-based cell protrusions that are formed by detached tumor cells. Here, we report that the formation of tumor cell microtentacles depends on the presence and dynamics of guanine nucleotide-binding proteins of the septin family, which are part of the cytoskeleton. In matrix-attached breast, lung, prostate and pancreas cancer cells, septins are associated with ...

2017
Pradeep Bandaru Neel H Shah Moitrayee Bhattacharyya John P Barton Yasushi Kondo Joshua C Cofsky Christine L Gee Arup K Chakraborty Tanja Kortemme Rama Ranganathan John Kuriyan

Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequenc...

Journal: :The Journal of chemical physics 2006
Robert L Jack Juan P Garrahan David Chandler

In a recent article [M. Merolle et al., Proc. Natl. Acad. Sci. U.S.A. 102, 10837 (2005)], it was argued that dynamic heterogeneity in d-dimensional glass formers is a manifestation of an order-disorder phenomenon in the d+1 dimensions of space time. By considering a dynamical analog of the free energy, evidence was found for phase coexistence between active and inactive regions of space time, a...

2017
Marina Diskowski Ahmad Reza Mehdipour Dorith Wunnicke Deryck J Mills Vedrana Mikusevic Natalie Bärland Jan Hoffmann Nina Morgner Heinz-Jürgen Steinhoff Gerhard Hummer Janet Vonck Inga Hänelt

Ion channel gating is essential for cellular homeostasis and is tightly controlled. In some eukaryotic and most bacterial ligand-gated K+ channels, RCK domains regulate ion fluxes. Until now, a single regulatory mechanism has been proposed for all RCK-regulated channels, involving signal transduction from the RCK domain to the gating area. Here, we present an inactive ADP-bound structure of Ktr...

Journal: :Neuron 2014
Taro Toyoizumi Megumi Kaneko Michael P. Stryker Kenneth D. Miller

Hebbian and homeostatic plasticity together refine neural circuitry, but their interactions are unclear. In most existing models, each form of plasticity directly modifies synaptic strength. Equilibrium is reached when the two are inducing equal and opposite changes. We show that such models cannot reproduce ocular dominance plasticity (ODP) because negative feedback from the slow homeostatic p...

2013
Derek A. Applewhite Kyle D. Grode Mara C. Duncan Stephen L. Rogers

Actin and microtubule dynamics must be precisely coordinated during cell migration, mitosis, and morphogenesis--much of this coordination is mediated by proteins that physically bridge the two cytoskeletal networks. We have investigated the regulation of the Drosophila actin-microtubule cross-linker Short stop (Shot), a member of the spectraplakin family. Our data suggest that Shot's cytoskelet...

2012
Jad Walters Joshua L. Schipper Paul Swartz Carla Mattos A. Clay Clark

A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to His266 at two sites in the interface, E124A and Y197C. We present results from X-ray crystallography, enzyma...

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