IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48403-0.html
   My bibliography  Save this article

Copper(I)-nitrene platform for chemoproteomic profiling of methionine

Author

Listed:
  • Samrat Sahu

    (Emory University)

  • Benjamin Emenike

    (Emory University)

  • Christian Michel Beusch

    (Emory University
    Uppsala University)

  • Pritha Bagchi

    (Emory University)

  • David Ezra Gordon

    (Emory University)

  • Monika Raj

    (Emory University)

Abstract

Methionine plays a critical role in various biological and cell regulatory processes, making its chemoproteomic profiling indispensable for exploring its functions and potential in protein therapeutics. Building on the principle of rapid oxidation of methionine, we report Copper(I)-Nitrene Platform for robust, and selective labeling of methionine to generate stable sulfonyl sulfimide conjugates under physiological conditions. We demonstrate the versatility of this platform to label methionine in bioactive peptides, intact proteins (6.5-79.5 kDa), and proteins in complex cell lysate mixtures with varying payloads. We discover ligandable proteins and sites harboring hyperreactive methionine within the human proteome. Furthermore, this has been utilized to profile oxidation-sensitive methionine residues, which might increase our understanding of the protective role of methionine in diseases associated with elevated levels of reactive oxygen species. The Copper(I)-Nitrene Platform allows labeling methionine residues in live cancer cells, observing minimal cytotoxic effects and achieving dose-dependent labeling. Confocal imaging further reveals the spatial distribution of modified proteins within the cell membrane, cytoplasm, and nucleus, underscoring the platform’s potential in profiling the cellular interactome.

Suggested Citation

  • Samrat Sahu & Benjamin Emenike & Christian Michel Beusch & Pritha Bagchi & David Ezra Gordon & Monika Raj, 2024. "Copper(I)-nitrene platform for chemoproteomic profiling of methionine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48403-0
    DOI: 10.1038/s41467-024-48403-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48403-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48403-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Michael T. Taylor & Jennifer E. Nelson & Marcos G. Suero & Matthew J. Gaunt, 2018. "A protein functionalization platform based on selective reactions at methionine residues," Nature, Nature, vol. 562(7728), pages 563-568, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Mengzhun Guo & Kai Zhao & Liang Guo & Rui Zhou & Qiuju He & Kuan Lu & Tian Li & Dandan Liu & Jinfeng Chen & Jing Tang & Xin Fu & Jinyun Zhou & Bei Zheng & Samuel I. Mann & Yongdeng Zhang & Jing Huang , 2023. "Copper assisted sequence-specific chemical protein conjugation at a single backbone amide," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Luke J. Dowman & Sameer S. Kulkarni & Juan V. Alegre-Requena & Andrew M. Giltrap & Alexander R. Norman & Ashish Sharma & Liliana C. Gallegos & Angus S. Mackay & Adarshi P. Welegedara & Emma E. Watson , 2022. "Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48403-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.