Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human H1R in complex with a Gq protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for Gq engagement in a model of “squash to activate and expand to deactivate”. The structure also reveals features for Gq coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of Gq/11 protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines.
A high quantum yield (4.3%) hybrid nanogel system based on engineered polypeptides and AgS quantum dots has been developed as a multifunctional diagnostic and therapeutic agent for targeted second near-infrared fluorescence, photoacoustic imaging, and photothermal therapy.
Recent progress in real-time spectral interferometry enables access to the internal dynamics of optical multisoliton complexes. Here, we report on the first, to the best of our knowledge, experimental observation of shaking soliton molecules by means of the dispersive Fourier transform technique. Beyond the simplex vibrating soliton pairs, multiple oscillatory motions can jointly involve in the internal dynamics, reminiscent of the shaking soliton pairs. Both quasi-periodically and chaotically evolving phase oscillations are approached in the sense of different oscillatory frequencies. In addition, the shaking soliton pair combined with sliding phase dynamics is also observed, and is interpreted as the superposition of two different internal motions. All of these results shed new light on the internal dynamics of soliton molecules with higher degrees of freedom, as well as enrich the framework toward multisoliton complexes.
The evolution of soliton molecules emphasizes the complex soliton dynamics akin to matter molecules. Beyond the simplest soliton molecule—a soliton pair constituted by two bound pulses—soliton molecules with more constituents have more degrees of freedom because of the temporal pulse separations and relative phases. Here we detailedly characterize the transient dynamics of soliton triplets in fiber lasers by using the dispersive Fourier transform measurement. A particular form of leading, central, and tailing pulses is constructed to shed new light on more intriguing scenarios and fuel the molecular analogy. Especially the vibrating dynamics of the central and tailing pulses are captured near the regime of equally spaced soliton triplets, which is reminiscent of the recurrent timing jitters within multi-pulse structures. Further insights enable access into a universal form of unequally spaced soliton triplets interpreted as
2
+
1
soliton molecules. Different binding strengths of intramolecular and intermolecular bonds are validated with respect to the diverse internal motions involved in this soliton triplet molecule. All these findings unveil the transient dynamics with more degrees of freedom as well as highlight the possible application for all-optical bit storage.
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