22 research outputs found

    Structural plasticity enables evolution and innovation of rubisco assemblies

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    Oligomerization is a core structural feature that defines the form and function of many proteins. Most proteins form molecular complexes; however, there remains a dearth of diversity-driven structural studies investigating the evolutionary trajectory of these assemblies. Rubisco is one such enzyme that adopts multiple assemblies, though the origins and distribution of its different oligomeric states remain cryptic. Here, we retrace the evolution of ancestral and extant form II rubiscos, revealing a complex and diverse history of oligomerization. We structurally characterize a novel tetrameric rubisco, elucidating how solvent-exposed surfaces can readily adopt new interactions to interconvert or give rise to new oligomeric states. We further use these principles to engineer and demonstrate how changes in oligomerization can be mediated by relatively few mutations. Our findings yield insight into how structural plasticity may give rise to new oligomeric states

    Simulation of Left Atrial Function Using a Multi-Scale Model of the Cardiovascular System

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    During a full cardiac cycle, the left atrium successively behaves as a reservoir, a conduit and a pump. This complex behavior makes it unrealistic to apply the time-varying elastance theory to characterize the left atrium, first, because this theory has known limitations, and second, because it is still uncertain whether the load independence hypothesis holds. In this study, we aim to bypass this uncertainty by relying on another kind of mathematical model of the cardiac chambers. In the present work, we describe both the left atrium and the left ventricle with a multi-scale model. The multi-scale property of this model comes from the fact that pressure inside a cardiac chamber is derived from a model of the sarcomere behavior. Macroscopic model parameters are identified from reference dog hemodynamic data. The multi-scale model of the cardiovascular system including the left atrium is then simulated to show that the physiological roles of the left atrium are correctly reproduced. This include a biphasic pressure wave and an eight-shaped pressure-volume loop. We also test the validity of our model in non basal conditions by reproducing a preload reduction experiment by inferior vena cava occlusion with the model. We compute the variation of eight indices before and after this experiment and obtain the same variation as experimentally observed for seven out of the eight indices. In summary, the multi-scale mathematical model presented in this work is able to correctly account for the three roles of the left atrium and also exhibits a realistic left atrial pressure-volume loop. Furthermore, the model has been previously presented and validated for the left ventricle. This makes it a proper alternative to the time-varying elastance theory if the focus is set on precisely representing the left atrial and left ventricular behaviors
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