Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

Sahoo, Bikash R.; Maruyama, Kei; Edula, Jyotheeswara R.; Tougan, Takahiro; Lin, Yuxi; Lee, Young-Ho; Horii, Toshihiro; Fujiwara, Toshimichi

doi:10.1038/srep44781

Cited by 12 publications

(8 citation statements)

References 54 publications

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“…Sahoo et al . studied the interaction between bovine myeloid matured cathelicidin-5 (BMAP-28) and large unilamellar vesicles ( 28 ). Terakawa et al .…”

Section: Resultsmentioning

confidence: 99%

BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra

Micsonai

Wien

Bulyáki

et al. 2018

Nucleic Acids Research

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890

786

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Circular dichroism (CD) spectroscopy is a widely used method to study the protein secondary structure. However, for decades, the general opinion was that the correct estimation of β-sheet content is challenging because of the large spectral and structural diversity of β-sheets. Recently, we showed that the orientation and twisting of β-sheets account for the observed spectral diversity, and developed a new method to estimate accurately the secondary structure (PNAS, 112, E3095). BeStSel web server provides the Beta Structure Selection method to analyze the CD spectra recorded by conventional or synchrotron radiation CD equipment. Both normalized and measured data can be uploaded to the server either as a single spectrum or series of spectra. The originality of BeStSel is that it carries out a detailed secondary structure analysis providing information on eight secondary structure components including parallel-β structure and antiparallel β-sheets with three different groups of twist. Based on these, it predicts the protein fold down to the topology/homology level of the CATH protein fold classification. The server also provides a module to analyze the structures deposited in the PDB for BeStSel secondary structure contents in relation to Dictionary of Secondary Structure of Proteins data. The BeStSel server is freely accessible at http://bestsel.elte.hu.

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“…Sahoo et al . studied the interaction between bovine myeloid matured cathelicidin-5 (BMAP-28) and large unilamellar vesicles ( 28 ). Terakawa et al .…”

Section: Resultsmentioning

confidence: 99%

BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra

Micsonai

Wien

Bulyáki

et al. 2018

Nucleic Acids Research

Self Cite

890

786

View full text Add to dashboard Cite

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“…The MD systems were subjected to a NaCl concentration of 100 mM and neutralized by adding requisite counterions. The equilibration of MD systems was achieved using NVT and NPT ensembles at 310 K and 1 bar using typical parameters described in our prior report . A production MD run of 100 ns was considered for structural and dynamic interpretation.…”

Section: Methodsmentioning

confidence: 99%

Diverse Structural Conversion and Aggregation Pathways of Alzheimerʼs Amyloid-β (1–40)

et al. 2019

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Complex amyloid aggregation of amyloid-β (1–40) (Aβ1–40) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aβ1–40 aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of Aβ1–40 induced by low solvent polarity accelerated cytotoxic Aβ1–40 amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of β-structure-rich protofibrils or oligomers via aggregation-prone helical structures. Modulation of the pH and salt concentration transformed oligomers to protofibrils, which proceeded to amyloid formation. We reveal diverse molecular mechanisms underlying Aβ1–40 aggregation with conceptual energy diagrams and propose that aggregation-prone partial helical structures are key to inducing amyloidogenesis. We demonstrate that context-dependent protein aggregation is comprehensively understood using the macroscopic phase diagram, which provides general insights into differentiation of amyloid formation and phase separation from unfolded and folded structures.

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“…The area of lipid membrane per binding Gd 3+ ion of 0.4 nm 2 is close to the area per lipid molecule of 0.6 nm 2 [31,46]. Since only about a quarter of phospholipids in E. coli are known to have negative charges [47], Gd 3+ ions would bind to not only anionic head groups of phospholipids [36,37] but also phosphates of neutral lipids and negatively charged biomolecules in the membranes and periplasm. The 13 C-NMR spectra supported the interaction mode of Gd 3+ with E. coli cells (Figure 4).…”

Section: Interaction Of Gd Complexes With the Cells And Cytotoxicitymentioning

confidence: 66%

Gadolinium Complexes as Contrast Agent for Cellular NMR Spectroscopy

Sakol

Egawa

Fujiwara

2020

IJMS

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Aqua Gd3+ and Gd-DOTA (gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacete) complexes were studied as a contrast agent in cellular NMR (nuclear magnetic resonance) spectroscopy for distinguishing between intracellular and extracellular spaces. The contrast agents for this purpose should provide strong paramagnetic relaxation enhancement and localize in the extracellular space without disturbing biological functions. Cell membrane permeability to Gd complexes was evaluated from the concentrations of gadolinium complexes in the inside and outside of E. coli cells measured by the 1H-NMR relaxation. The site-specific binding of the complexes to E. coli cells was also analyzed by high-resolution solid-state 13C-NMR. The aqua Gd3+ complex did not enhance T1 relaxation in proportion to the amount of added Gd3+. This Gd3+ concentration dependence and the 13C-NMR indicated that its strong cytotoxicity should be due to the binding of the paramagnetic ions to cellular components especially at the lipid membranes. In contrast, Gd-DOTA stayed in the solution states and enhanced relaxation in proportion to the added amount. This agent exhibited strong T1 contrast between the intra- and extracellular spaces by a factor of ten at high concentrations under which the cells were viable over a long experimental time of days. These properties make Gd-DOTA suitable for selectively contrasting the living cellular space in NMR spectroscopy primarily owing to its weak interaction with cellular components.

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Mechanistic and structural basis of bioengineered bovine Cathelicidin-5 with optimized therapeutic activity

Cited by 12 publications

References 54 publications

BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra

BeStSel: a web server for accurate protein secondary structure prediction and fold recognition from the circular dichroism spectra

Diverse Structural Conversion and Aggregation Pathways of Alzheimerʼs Amyloid-β (1–40)

Gadolinium Complexes as Contrast Agent for Cellular NMR Spectroscopy

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