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Direct visualization of conformational dynamics of hemagglutinin and interaction between hemagglutinin and exosomes using high-speed atomic force microscopy.

Research Project

Project/Area Number 19K23841
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0803:Pathology, infection/immunology, and related fields
Research InstitutionKanazawa University

Principal Investigator

Lim Kee Siang  金沢大学, ナノ生命科学研究所, 特任助教 (60842987)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsHemagglutinin / Influenza A / HS-AFM / Fusogenic transition / viral fusion protein / Influenz A / Virulence factor / High Speed AFM / Exosome
Outline of Research at the Start

Generation of HS-AFM simulated images of HA using data in RCSB PDB website.

HS-AFM recording for HA native structure and molecular dynamic in physiological buffers.

Direct visualization of transient conformational changes of HA in acidic conditions using HS-AFM.

Outline of Final Research Achievements

The native conformation of human influenza A hemagglutinin (HA) observed using HS-AFM is ellipsoidal, and it undergoes fusogenic transition in acidic condition to become Y-shape. Direct real-time observation of fusogenic transition suggests that the transition mechanism is likely to fit to the Uncaging Model. HA-exosome interaction is weak in neutral condition but firm in acidic condition. The weak interaction could be mediated by HA-receptor (sialic acid) interaction. In contrast, the firm interaction implies that HA fusion peptide could be released after fusogenic transition, and then inserted into exosomal layer and resulted deformation or rupture of exosomes.

Academic Significance and Societal Importance of the Research Achievements

This study could provide important insights that are essential for vaccine and antiviral drug developments to cope annual flu season in Japan. Besides, our study also suggest that HS-AFM is a feasible tool to complement other imaging tools and bioassays to enhance virology research in near future.

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2020 2019

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (4 results)

  • [Journal Article] High-Speed AFM Reveals Molecular Dynamics of Human Influenza A Hemagglutinin and Its Interaction with Exosomes2020

    • Author(s)
      Lim Keesiang、Kodera Noriyuki、Wang Hanbo、Mohamed Mahmoud Shaaban、Hazawa Masaharu、Kobayashi Akiko、Yoshida Takeshi、Hanayama Rikinari、Yano Seiji、Ando Toshio、Wong Richard W.
    • Journal Title

      Nano Letters

      Volume: 20 Issue: 9 Pages: 6320-6328

    • DOI

      10.1021/acs.nanolett.0c01755

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] High-Speed AFM Reveals Molecular Dynamics of Human Influenza A Hemagglutinin and Its Interaction with Exosomes2020

    • Author(s)
      Lim Kee Siang
    • Organizer
      MBSJ (The Molecular Biology Society of Japan) 2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] High-Speed AFM Reveals Molecular Dynamics of Human Influenza A Hemagglutinin and Its Interaction with Exosomes2020

    • Author(s)
      Lim Kee Siang
    • Organizer
      WPI NanoLSI Symposium (4th)
    • Related Report
      2020 Annual Research Report
  • [Presentation] Direct visualization of avian influenza H5N1 hemagglutinin precursor and its conformational changes by high-speed atomic force microscopy.2020

    • Author(s)
      Lim Kee Siang
    • Organizer
      1st WPI NanoLSI-iCeMS Joint Symposium on Nanoimaging and Advanced Materials for Life Science
    • Related Report
      2019 Research-status Report
  • [Presentation] Direct visualization of avian influenza H5N1 Hemagglutinin precursor and its conformational change by high-speed atomic force microscopy.2019

    • Author(s)
      Lim Kee Siang
    • Organizer
      MBSJ
    • Related Report
      2019 Research-status Report

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Published: 2019-09-03   Modified: 2022-01-27  

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