Many membrane receptors are regulated by nutrients. However, how these nutrients control a single receptor remains unknown, even in the case of the well-studied calcium-sensing receptor CaSR, which is regulated by multiple factors, including ions and amino acids. Here, we developed an innovative cell-free Förster resonance energy transfer (FRET)-based conformational CaSR biosensor to clarify the main conformational changes associated with activation. By allowing a perfect control of ambient nutrients, this assay revealed that Ca2+ alone fully stabilizes the active conformation, while amino acids behave as pure positive allosteric modulators. Based on the identification of Ca2+ activation sites, we propose a molecular basis for how these different ligands cooperate to control CaSR activation. Our results provide important information on CaSR function and improve our understanding of the effects of genetic mutations responsible for human diseases. They also provide insights into how a receptor can integrate signals from various nutrients to better adapt to the cell response.
A one-step and energy-saving method was proposed to synthesize hierarchical and hollow Co(VO)-Co(OH) composite leaf arrays on carbon cloth, which expressed high capacitance (522 mF cm or 803 F g at the current density of 0.5 mA cm), good rate capability (79.5% capacitance retention after a 30-fold increase of the current density) and excellent cycling stability (90% capacitance retention after 15 000 charge-discharge cycles) when tested as a supercapacitor electrode.
Through
the combination of transient spectroscopy and theoretical
simulations, an accelerated singlet fission (SF) process was evidently
observed in the strongly coupled H-type-like aggregation thin films
of a dipyrrolonaphthyridinedione skeleton. Results elucidate that
in this H-type-like aggregation, the substantially stabilized charge
transfer (CT) state is close in energy with singlet and excimer states,
resulting in a CT/excimer mixed state, which could drive excited-state
population escaping from excimer trap and promote an ultrafast and
highly efficient SF process. Our results not only enrich the limited
capacity of SF materials but also contribute to an in-depth understanding
of SF dynamics in H-type aggregation, which is of fundamental importance
for designing new SF sensitizers and implementing practical SF applications.
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