Crystal Structure of a Multi-Domain Human Smoothened Receptor in Complex With a Super Stabilizing Ligand

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The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

Date Created
2017-05-17
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Fabrication and characterization of metallic cavity nanolasers

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Nanolasers represents the research frontier in both the areas of photonics and nanotechnology for its interesting properties in low dimension physics, its appealing prospects in integrated photonics, and other on-chip applications. In this thesis, I present my research work on

Nanolasers represents the research frontier in both the areas of photonics and nanotechnology for its interesting properties in low dimension physics, its appealing prospects in integrated photonics, and other on-chip applications. In this thesis, I present my research work on fabrication and characterization of a new type of nanolasers: metallic cavity nanolasers. The last ten years witnessed a dramatic paradigm shift from pure dielectric cavity to metallic cavity in the research of nanolasers. By using low loss metals such as silver, which is highly reflective at near infrared, light can be confined in an ultra small cavity or waveguide with sub-wavelength dimensions, thus enabling sub-wavelength cavity lasers. Based on this idea, I fabricated two different kinds of metallic cavity nanolasers with rectangular and circular geometries with InGaAs as the gain material and silver as the metallic shell. The lasing wavelength is around 1.55 μm, intended for optical communication applications. Continuous wave (CW) lasing at cryogenic temperature under current injection was achieved on devices with a deep sub-wavelength physical cavity volume smaller than 0.2 λ3. Improving device fabrication process is one of the main challenges in the development of metallic cavity nanolasers due to its ultra-small size. With improved fabrication process and device design, CW lasing at room temperature was demonstrated as well on a sub-wavelength rectangular device with a physical cavity volume of 0.67 λ3. Experiments verified that a small circular nanolasers supporting TE¬01 mode can generate an azimuthal polarized laser beam, providing a compact such source under electrical injection. Sources with such polarizations could have many special applications. Study of digital modulation of circular nanolasers showed that laser noise is an important factor that will affect the data rate of the nanolaser when used as the light source in optical interconnects. For future development, improving device fabrication processes is required to improve device performance. In addition, techniques need to be developed to realize nanolaser/Si waveguide integration. In essence, resolving these two critical issues will finally pave the way for these nanolasers to be used in various practical applications.
Date Created
2014
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