| 1. |
- Asami, Jinta, et al.
(författare)
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Structural basis of hepatitis B virus receptor binding
- 2024
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Ingår i: Nature Structural & Molecular Biology. - 1545-9993 .- 1545-9985. ; 31, s. 447-454
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV), a leading cause of developing hepatocellular carcinoma affecting more than 290 million people worldwide, is an enveloped DNA virus specifically infecting hepatocytes. Myristoylated preS1 domain of the HBV large surface protein binds to the host receptor sodium-taurocholate cotransporting polypeptide (NTCP), a hepatocellular bile acid transporter, to initiate viral entry. Here, we report the cryogenic-electron microscopy structure of the myristoylated preS1 (residues 2–48) peptide bound to human NTCP. The unexpectedly folded N-terminal half of the peptide embeds deeply into the outward-facing tunnel of NTCP, whereas the C-terminal half formed extensive contacts on the extracellular surface. Our findings reveal an unprecedented induced-fit mechanism for establishing high-affinity virus–host attachment and provide a blueprint for the rational design of anti-HBV drugs targeting virus entry.
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| 2. |
- Asami, Jinta, et al.
(författare)
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Structure of the bile acid transporter and HBV receptor NTCP
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 606:7916, s. 1021-1026
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with hepatitis B virus (HBV) affects more than 290 million people worldwide, is a major cause of cirrhosis and hepatocellular carcinoma, and results in an estimated 820,000 deaths annually. For HBV infection to be established, a molecular interaction is required between the large glycoproteins of the virus envelope (known as LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP), a sodium-dependent bile acid transporter from the blood to hepatocytes. However, the molecular basis for the virus–transporter interaction is poorly understood. Here we report the cryo-electron microscopy structures of human, bovine and rat NTCPs in the apo state, which reveal the presence of a tunnel across the membrane and a possible transport route for the substrate. Moreover, the cryo-electron microscopy structure of human NTCP in the presence of the myristoylated preS1 domain of LHBs, together with mutation and transport assays, suggest a binding mode in which preS1 and the substrate compete for the extracellular opening of the tunnel in NTCP. Our preS1 domain interaction analysis enables a mechanistic interpretation of naturally occurring HBV-insusceptible mutations in human NTCP. Together, our findings provide a structural framework for HBV recognition and a mechanistic understanding of sodium-dependent bile acid translocation by mammalian NTCPs.
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| 3. |
- Xie, Zhibin, et al.
(författare)
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Highly efficient dye-sensitized solar cells using phenothiazine derivative organic dyes
- 2010
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Ingår i: Progress in Photovoltaics. - : John Wiley & Sons. - 1062-7995 .- 1099-159X. ; 18:8, s. 573-581
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Tidskriftsartikel (refereegranskat)abstract
- Two novel organic dyes have been synthesized using electron rich phenothiazine as electron donors and oligothiophene vinylene as conjugation spacers. The two dyes (2E)-2-cyano-3-(5-(5-((E)-2-(10-(2-ethylhexyl)-10H-phenothiazin-7-yl)vinyl)thiophen-2-yl)thiophen-2-yl)acrylic acid (PTZ-1) and (2E)-3-(5-(5-(4,5-bis((E)-2-(10-(2-ethylhexyl)-10H-phenothiazin-3-yl)vinyl)thiophen-2-yl)thiophen-2-yl)thiophen-2-yl)-2-cyanoacrylic acid (PTZ-2) were fully characterized and employed in dye-sensitized solar cells (DSCs) to explore the effect of disubstituted donors on photovoltaic (PV) performance. The solar cells sensitized by the PTZ1 dye have a high IPCE plateau of 80% and achieve a short-circuit photocurrent density of 12.98 mA/cm2, an open-circuit voltage of 0.713 V, and a fill factor (ff) of 66.6%, corresponding to a conversion efficiency of 6.17% under AM 1.5 100 mW/cm2 illumination. The different performance of the solar cells based on the two dyes can be understood from the studies of the electron kinetics by electrochemical impedance spectroscopy (EIS). These investigations reveal that disubstituted donors in the organic sensitizers of three or more conjugation units deteriorate the PV performance due to enhanced recombination.
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