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Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle

Author

Listed:
  • Emily C. Hartman

    (University of California)

  • Christopher M. Jakobson

    (University of California
    Stanford University School of Medicine)

  • Andrew H. Favor

    (University of California)

  • Marco J. Lobba

    (University of California)

  • Ester Álvarez-Benedicto

    (University of California)

  • Matthew B. Francis

    (University of California
    Lawrence Berkeley National Laboratories)

  • Danielle Tullman-Ercek

    (Northwestern University)

Abstract

Self-assembling proteins are critical to biological systems and industrial technologies, but predicting how mutations affect self-assembly remains a significant challenge. Here, we report a technique, termed SyMAPS (Systematic Mutation and Assembled Particle Selection), that can be used to characterize the assembly competency of all single amino acid variants of a self-assembling viral structural protein. SyMAPS studies on the MS2 bacteriophage coat protein revealed a high-resolution fitness landscape that challenges some conventional assumptions of protein engineering. An additional round of selection identified a previously unknown variant (CP[T71H]) that is stable at neutral pH but less tolerant to acidic conditions than the wild-type coat protein. The capsids formed by this variant could be more amenable to disassembly in late endosomes or early lysosomes—a feature that is advantageous for delivery applications. In addition to providing a mutability blueprint for virus-like particles, SyMAPS can be readily applied to other self-assembling proteins.

Suggested Citation

  • Emily C. Hartman & Christopher M. Jakobson & Andrew H. Favor & Marco J. Lobba & Ester Álvarez-Benedicto & Matthew B. Francis & Danielle Tullman-Ercek, 2018. "Quantitative characterization of all single amino acid variants of a viral capsid-based drug delivery vehicle," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03783-y
    DOI: 10.1038/s41467-018-03783-y
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    Cited by:

    1. Carolyn E. Mills & Curt Waltmann & Andre G. Archer & Nolan W. Kennedy & Charlotte H. Abrahamson & Alexander D. Jackson & Eric W. Roth & Sasha Shirman & Michael C. Jewett & Niall M. Mangan & Monica Olv, 2022. "Vertex protein PduN tunes encapsulated pathway performance by dictating bacterial metabolosome morphology," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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