한국동물위생학회지 (Korean Journal of Veterinary Service)

  • 제44권4호
  • /
  • Pages.185-194
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  • 2021
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  • 3022-7372(pISSN)
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  • 2287-7630(eISSN)
한국동물위생학회 (The Korean Society of Veterinary Service)
권호 표지
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Characterization of binding specificity using GST-conjugated mutant huntingtin epitopes in surface plasmon resonance (SPR)

  • Cho, Hang-Hee (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Kim, Tae Hoon (Department of Food Science and Biotechnology, Daegu University) ;
  • Kim, Hong-Duck (Department of Public Health (Division of Environmental Health Science), New York Medical College) ;
  • Cho, Jae-Hyeon (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
  • 투고 : 2021.09.03
  • 심사 : 2021.11.24
  • 발행 : 2021.12.30
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초록

Polyglutamine extension in the coding sequence of mutant huntingtin causes neuronal degeneration associated with the formation of insoluble polyglutamine aggregates in Huntington's disease (HD). Mutant huntingtin can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. To better understand the mechanism by which an elongated polyglutamine causes aggregates, we have developed an in vitro binding assay system of polyglutamine tract from truncated huntingtin. We made GST-HD exon1 fusion proteins which have expanded polyglutamine epitopes (e.g., 17, 23, 32, 46, 60, 78, 81, and 94 CAG repeats). In the present emergence of new study adjusted nanotechnology on protein chip such as surface plasmon resonance strategy which used to determine the substance which protein binds in drug discovery platform is worth to understand better neurodegenerative diseases (i.e., Alzheimer disease, Parkinson disease and Huntington disease) and its pathogenesis along with development of therapeutic measures. Hence, we used strengths of surface plasmon resonance (SPR) technology which is enabled to examine binding specificity and explore targeted molecular epitope using its electron charged wave pattern in HD pathogenesis utilize conjugated mutant epitope of HD protein and its interaction whether wild type GST-HD interacts with mutant GST-HD with maximum binding affinity at pH 6.85. We found that the maximum binding affinity of GST-HD17 with GST-HD81 was higher than the binding affinities of GST-HD17 with other mutant GST-HD constructs. Furthermore, our finding illustrated that the mutant form of GST-HD60 showed a stronger binding to GST-HD23 or GST-HD17 than GST-HD60 or GST-HD81. These results indicate that the binding affinity of mutant huntingtin does not correlate with the length of polyglutamine. It suggests that the aggregation of an expanded polyglutamine might have easily occurred in the presence of wild type form of huntingtin.

키워드

과제정보

This research was supported in part by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2020R1F1A104896911).

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