Transforming the Domain Structure of Botulinum Neurotoxins into Novel Therapeutics

Botulinum neurotoxins (BoNTs) are categorised into immunologically distinct serotypes BoNT/A to /G). Each serotype can also be further divided into subtypes based on differences in amino acid sequence. BoNTs are ~150 kDa proteins comprised of three major functional domains: an N-terminal zinc metalloprotease light chain (LC), a translocation domain (HN), and a binding domain (HC). The HC is responsible for targeting the BoNT to the neuronal cell membrane, and each serotype has evolved to bind via different mechanisms to different target receptors. Most structural characterisations to date have focussed on the first identified subtype within each serotype (e.g., BoNT/A1). Subtype differences within BoNT serotypes can affect intoxication, displaying different botulism symptoms in vivo, and less emphasis has been placed on investigating these variants. This review outlines the receptors for each BoNT serotype and describes the basis for the highly specific targeting of neuronal cell membranes. Understanding receptor binding is of vital importance, not only for the generation of novel therapeutics but also for understanding how best to protect from intoxication.

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Novel therapeutics based on recombinant botulinum neurotoxins to normalize the release of transmitters and pain mediators

FEBS Journal ◽

10.1111/j.1742-4658.2011.08205.x ◽

2011 ◽

Vol 278 (23) ◽

pp. 4454-4466 ◽

Cited By ~ 33

Author(s):

J. Oliver Dolly ◽

Jiafu Wang ◽

Tomas H. Zurawski ◽

Jianghui Meng

Keyword(s):

Novel Therapeutics ◽

Botulinum Neurotoxins

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Domains and domain nucleation in magnetron-sputtered CoCr thin films

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100151064 ◽

1993 ◽

Vol 51 ◽

pp. 1046-1047

Author(s):

B. G. Demczyk

Keyword(s):

Thin Films ◽

Domain Structure ◽

Magnetic Domain ◽

Domain Size ◽

Film Plane ◽

Magnetic Domain Structure ◽

Perpendicular Magnetization ◽

Columnar Grains ◽

Reversal Mechanism ◽

Lorentz Transmission Electron Microscopy

CoCr thin films have been of interest for a number of years due to their strong perpendicular anisotropy, favoring magnetization normal to the film plane. The microstructure and magnetic properties of CoCr films prepared by both rf and magnetron sputtering have been examined in detail. By comparison, however, relatively few systematic studies of the magnetic domain structure and its relation to the observed film microstructure have been reported. In addition, questions still remain as to the operative magnetization reversal mechanism in different film thickness regimes. In this work, the magnetic domain structure in magnetron sputtered Co-22 at.%Cr thin films of known microstructure were examined by Lorentz transmission electron microscopy. Additionally, domain nucleation studies were undertaken via in-situ heating experiments.It was found that the 50 nm thick films, which are comprised of columnar grains, display a “dot” type domain configuration (Figure 1d), characteristic of a perpendicular magnetization. The domain size was found to be on the order of a few structural columns in diameter.

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Ferroelectric Domain Structure of Pb(Zr.52Ti.48)03

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600000933 ◽

1980 ◽

Vol 38 ◽

pp. 214-215

Author(s):

E.K. Goo ◽

R.K. Mishra

Keyword(s):

Phase Transformation ◽

Domain Structure ◽

Tetragonal Phase ◽

Ferroelectric Domain ◽

Cubic Phase ◽

Ion Milling ◽

Thin Foils ◽

Ferroelectric Domain Structure ◽

Ferroelectric Domains

Ferroelectric domains are twins that are formed when PZT undergoes a phase transformation from a non-ferroelectric cubic phase to a ferroelectric tetragonal phase upon cooling below ∼375°C.,1 The tetragonal phase is spontaneously polarized in the direction of c-axis, making each twin a ferroelectric domain. Thin foils of polycrystalline Pb (Zr.52Ti.48)03 were made by ion milling and observed in the Philips EM301 with a double tilt stage.

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