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Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide

Overview of attention for article published in Journal of Nanobiotechnology, April 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (79th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

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1 X user
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2 patents
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2 Wikipedia pages

Citations

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Title
Enhanced stability of a chimeric hepatitis B core antigen virus-like-particle (HBcAg-VLP) by a C-terminal linker-hexahistidine-peptide
Published in
Journal of Nanobiotechnology, April 2018
DOI 10.1186/s12951-018-0363-0
Pubmed ID
Authors

Jens Schumacher, Tijana Bacic, René Staritzbichler, Matin Daneschdar, Thorsten Klamp, Philipp Arnold, Sabrina Jägle, Özlem Türeci, Jürgen Markl, Ugur Sahin

Abstract

Virus-like-particles (VLPs) are attractive nanoparticulate scaffolds for broad applications in material/biological sciences and medicine. Prior their functionalization, specific adaptations have to be carried out. These adjustments frequently lead to disordered particles, but the particle integrity is an essential factor for the VLP suitability. Therefore, major requirements for particle stabilization exist. The objective of this study was to evaluate novel stabilizing elements for functionalized chimeric hepatitis B virus core antigen virus-like particles (HBcAg-VLP), with beneficial characteristics for vaccine development, imaging or delivery. The effects of a carboxy-terminal polyhistidine-peptide and an intradimer disulfide-bridge on the stability of preclinically approved chimeric HBcAg-VLPs were assessed. We purified recombinant chimeric HBcAg-VLPs bearing different modified C-termini and compared their physical and chemical particle stability by quantitative protein-biochemical and biophysical techniques. We observed lower chemical resistance of T = 3- compared to T = 4-VLP (triangulation number) capsids and profound impairment of accessibility of hexahistidine-peptides in assembled VLPs. Histidines attached to the C-terminus were associated with superior mechanical and/or chemical particle stability depending on the number of histidine moieties. A molecular modeling approach based on cryo-electron microscopy and biolayer interferometry revealed the underlying structural mechanism for the strengthening of the integrity of VLPs. Interactions triggering capsid stabilization occur on a highly conserved residue on the basis of HBcAg-monomers as well as on hexahistidine-peptides of adjacent monomers. This new stabilization mechanism appears to mimic an evolutionary conserved stabilization concept for hepadnavirus core proteins. These findings establish the genetically simply transferable C-terminal polyhistidine-peptide as a general stabilizing element for chimeric HBcAg-VLPs to increase their suitability.

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X Demographics

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 82 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 82 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 16%
Student > Ph. D. Student 13 16%
Student > Master 12 15%
Student > Bachelor 10 12%
Student > Doctoral Student 3 4%
Other 8 10%
Unknown 23 28%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 19 23%
Agricultural and Biological Sciences 10 12%
Chemistry 7 9%
Immunology and Microbiology 6 7%
Medicine and Dentistry 4 5%
Other 13 16%
Unknown 23 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 September 2022.
All research outputs
#3,270,010
of 23,419,482 outputs
Outputs from Journal of Nanobiotechnology
#110
of 1,506 outputs
Outputs of similar age
#67,139
of 328,992 outputs
Outputs of similar age from Journal of Nanobiotechnology
#2
of 20 outputs
Altmetric has tracked 23,419,482 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,506 research outputs from this source. They receive a mean Attention Score of 3.6. This one has done particularly well, scoring higher than 92% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,992 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.