• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.191-199
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• 1992

Selective quenching of 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups was utilized to examine the transbilayer fluidity asymmetry of model membranes of total lipids (SPMVTL) extracted from synaptosomal plasma membrane vesicles (SPMV). The polarization (P), anisotropy (r), limiting anisotropy $(r_{\infty})$, and order parameter (S) of DPH in the inner monolayer were 0.031, 0.025, 0.033, and 0.070, respectively, greater than calculated for the outer monolayer of SPMVTL. Selective quenching of DPH by trinitrophenyl groups was also utilized to examine the effects of n-alkanols on the individual monolayer structure of SPMVTL. n-Alkanols fluidized the hydrocarbon region of bulk SPMVTL, and the potencies of n-alkanols up to 1-nonanol increased with carbon chain length. It appears that the potencies in bilayer fluidization increase by 1 order of magnitude as the carbon chain length increases by two carbon atoms. The cut-off phenomenon was reached at 1-decanol, where further increase in hydrocarbon length resulted in a decrease in pharmacological activity. The n-alkanols had greater fluidizing effects on the outer monolayer as compared to the inner monolayer of SPMVTL, even though these selective effects tended to become weaker as carbon chain length increased. Thus, it has been proven that n-alkanols exhibit selective rather than nonselective fluidizing effects within transbilayer domains of SPMVTL.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.68-68
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• 2003

HP(2-20) (AKKVFKRLEKLEKLFSKIQNDK) derived from the N-terminus of Helicobacter pylori Ribosomal Protein L1 shows potent antimicrobial activity against bacterial, fungi and cancer cells without cytotoxic effect. In order to investigate the relationships between antimicrobial activity and the structures, several analogues have been designed and synthesized. The structures of these peptides in SDS micelles have been investigated using NMR spectroscopy and they revealed that analogue 3 has the longest, well-defined alpha-helix from Val5 to Trp19. NOESY experiments performed on HP and its analogues in nondeuterated SDS micelles show that protons in the indole ring of Trp16 are in close contact with methylene protons of SDS micelles. In order to probe the position of HP and its analogues relative to the SDS micelles, spin-labeled stearate was added. Large effects are observed for the chemical shifts and the intensities of Phe5, Glu9, Phe12, and Trp16 within the helix region by 16-doxylstearate. This result implies that 16-doxylstearate is located in the center of the micelles and the hydrophobic phase of the amphiphilic ${\alpha}$-helix is located in contact with the acyl chains of the micelles. Also, Lys3 and Lys4 at N-terminus and Lys20 at C-terminus may produce an optimal arrangement for electrostatic interactions between the sulfate head groups of the SDS and the positively charged lysyl N$\sub$3/$\^$+/. Interactions between the indole ring of Trp and the membrane, as well as the amphiphilic ${\alpha}$-helical structure of HP induced by Trp at the C-terminus may allow HP to span the lipid bilayer. These structural features are crucial for their potent antibiotic activities.

• Molecules and Cells
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• v.39 no.4
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• pp.286-291
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• 2016

Epstein-Barr virus (EBV) is the prototypical ${\gamma}$-herpesvirus and an obligate human pathogen that infects mainly epithelial cells and B cells, which can result in malignancies. EBV infects these target cells by fusing with the viral and cellular lipid bilayer membranes using multiple viral factors and host receptor(s) thus exhibiting a unique complexity in its entry machinery. To enter epithelial cells, EBV requires minimally the conserved core fusion machinery comprised of the glycoproteins gH/gL acting as the receptor-binding complex and gB as the fusogen. EBV can enter B cells using gp42, which binds tightly to gH/gL and interacts with host HLA class II, activating fusion. Previously, we published the individual crystal structures of EBV entry factors, such as gH/gL and gp42, the EBV/host receptor complex, gp42/HLA-DR1, and the fusion protein EBV gB in a postfusion conformation, which allowed us to identify structural determinants and regions critical for receptor-binding and membrane fusion. Recently, we reported different low resolution models of the EBV B cell entry triggering complex (gHgL/gp42/HLA class II) in "open" and "closed" states based on negative-stain single particle electron microscopy, which provide further mechanistic insights. This review summarizes the current knowledge of these key players in EBV entry and how their structures impact receptor-binding and the triggering of gB-mediated fusion.