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Exploring the structure and mechanism of formation of an artificial protein capsid, toward the development of a novel redox-responsive nano-carrier system

Research Project

Project/Area Number 25560231
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Malay Ali  国立研究開発法人理化学研究所, 環境資源科学研究センター, 研究員 (40467006)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsprotein cage / self-assembly / bionanotechnology / gold nanoparticle / metal coordination / artificial capsid / smart nanomaterial / supramolecular assembly / gold cluster / gold chemistry / self assembly / capsid / protein engineering / coordination chemistry / protein / synthetic biology / gold catalysis / cryo EM / drug delivery / protein structure / protein shell
Outline of Final Research Achievements

We present a new method for assembling protein cages with well-defined, symmetrical structures. The starting material, a mutated TRAP protein, folds into an 11-membered ring with cysteine residues on the outer surface. Reaction with the gold cluster Au55 leads to the formation of a hollow cage (TRAP-cage), which exhibits extreme stability, yet disassembles under reducing conditions. Potential applications in biomedicine (drug delivery) are suggested.
The TRAP-cage structure yielded unexpected results. Neighboring TRAP rings were linked by gold atoms coordinated via cysteines: TRAP-cage represents the first de novo assembled protein cage by metal coordination. Furthermore, with 264 protein subunits, TRAP-cage shows a unique symmetry. Instead of icosahedral symmetry, TRAP-cage has snub cube symmetry, with an 11mer ring occupying each of the 24 vertices with near-perfect regularity. Our findings suggest novel strategies for building large protein cages by exploring alternative symmetries.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Invited: 2 results)

  • [Journal Article] Probing structural dynamics of an artificial protein cage using high-speedatomic force microscopy2015

    • Author(s)
      M. Imamura, T. Uchihashi, T. Ando, A. Leifert, U. Simon, A. D. Malay and J. G. Heddle
    • Journal Title

      Nano Letters

      Volume: 15 Issue: 2 Pages: 1331-1335

    • DOI

      10.1021/nl5045617

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Bio-nanotechnology: engineering a redox-responsive supramolecular protein cage structure for drug delivery2014

    • Author(s)
      Ali Malay
    • Organizer
      University of the Philippines, College of Medicine
    • Place of Presentation
      Manila, Philippines
    • Year and Date
      2014-12-03
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Development of a nano-delivery system based on an engineered protein cage structure2014

    • Author(s)
      Ali Malay
    • Organizer
      Asia-Pacific International Molecular Biology Network (A-IMBN) 17th Annual Conference
    • Place of Presentation
      Manila, Philippines
    • Year and Date
      2014-12-01 – 2014-12-02
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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