IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35054-2.html
   My bibliography  Save this article

Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation

Author

Listed:
  • Henrik M. Hammarén

    (Genome Biology Unit)

  • Eva-Maria Geissen

    (Structural and Computational Biology Unit)

  • Clement M. Potel

    (Genome Biology Unit)

  • Martin Beck

    (Department of Molecular Sociology)

  • Mikhail M. Savitski

    (Genome Biology Unit)

Abstract

Post-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods relying on pulsed metabolic labeling are popular to quantify turnover rates on a proteome-wide scale. Such data have traditionally been interpreted in the context of protein proteolytic stability. Here, we combine theoretical kinetic modeling with experimental pulsed stable isotope labeling of amino acids in cell culture (pSILAC) for the study of protein phosphorylation. We demonstrate that metabolic labeling combined with PTM-specific enrichment does not measure effects of PTMs on protein stability. Rather, it reveals the relative order of PTM addition and removal along a protein’s lifetime—a fundamentally different metric. This is due to interconversion of the measured proteoform species. Using this framework, we identify temporal phosphorylation sites on cell cycle-specific factors and protein complex assembly intermediates. Our results thus allow tying PTMs to the age of the modified proteins.

Suggested Citation

  • Henrik M. Hammarén & Eva-Maria Geissen & Clement M. Potel & Martin Beck & Mikhail M. Savitski, 2022. "Protein-Peptide Turnover Profiling reveals the order of PTM addition and removal during protein maturation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35054-2
    DOI: 10.1038/s41467-022-35054-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35054-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-35054-2?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. Sara Cuylen-Haering & Mina Petrovic & Alberto Hernandez-Armendariz & Maximilian W. G. Schneider & Matthias Samwer & Claudia Blaukopf & Liam J. Holt & Daniel W. Gerlich, 2020. "Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly," Nature, Nature, vol. 587(7833), pages 285-290, November.
    2. Ana Martinez-Val & Dorte B. Bekker-Jensen & Sophia Steigerwald & Claire Koenig & Ole Østergaard & Adi Mehta & Trung Tran & Krzysztof Sikorski & Estefanía Torres-Vega & Ewa Kwasniewicz & Sólveig Hlín B, 2021. "Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    3. Toby Mathieson & Holger Franken & Jan Kosinski & Nils Kurzawa & Nico Zinn & Gavain Sweetman & Daniel Poeckel & Vikram S. Ratnu & Maike Schramm & Isabelle Becher & Michael Steidel & Kyung-Min Noh & Gio, 2018. "Systematic analysis of protein turnover in primary cells," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    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. Ji Min Lee & Henrik M. Hammarén & Mikhail M. Savitski & Sung Hee Baek, 2023. "Control of protein stability by post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Julia P. Schessner & Vincent Albrecht & Alexandra K. Davies & Pavel Sinitcyn & Georg H. H. Borner, 2023. "Deep and fast label-free Dynamic Organellar Mapping," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Tanveer Singh Batth & Marie Locard-Paulet & Nadezhda T. Doncheva & Blanca Lopez Mendez & Lars Juhl Jensen & Jesper Velgaard Olsen, 2024. "Streamlined analysis of drug targets by proteome integral solubility alteration indicates organ-specific engagement," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Roman Vetter & Dagmar Iber, 2022. "Precision of morphogen gradients in neural tube development," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    5. Simone Sanzo & Katrin Spengler & Anja Leheis & Joanna M. Kirkpatrick & Theresa L. Rändler & Tim Baldensperger & Therese Dau & Christian Henning & Luca Parca & Christian Marx & Zhao-Qi Wang & Marcus A., 2021. "Mapping protein carboxymethylation sites provides insights into their role in proteostasis and cell proliferation," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
    6. Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    7. Ziqi Liu & Fuhu Guo & Yufan Zhu & Shengnan Qin & Yuchen Hou & Haotian Guo & Feng Lin & Peng R. Chen & Xinyuan Fan, 2024. "Bioorthogonal photocatalytic proximity labeling in primary living samples," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Joanne Watson & Harriet R. Ferguson & Rosie M. Brady & Jennifer Ferguson & Paul Fullwood & Hanyi Mo & Katherine H. Bexley & David Knight & Gareth Howell & Jean-Marc Schwartz & Michael P. Smith & Chiar, 2022. "Spatially resolved phosphoproteomics reveals fibroblast growth factor receptor recycling-driven regulation of autophagy and survival," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    9. Feng Yuan & Yi Li & Xinyue Zhou & Peiyuan Meng & Peng Zou, 2023. "Spatially resolved mapping of proteome turnover dynamics with subcellular precision," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    10. Daniel P. Bondeson & Zachary Mullin-Bernstein & Sydney Oliver & Thomas A. Skipper & Thomas C. Atack & Nolan Bick & Meilani Ching & Andrew A. Guirguis & Jason Kwon & Carly Langan & Dylan Millson & Bren, 2022. "Systematic profiling of conditional degron tag technologies for target validation studies," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    11. Jana Zecha & Wassim Gabriel & Ria Spallek & Yun-Chien Chang & Julia Mergner & Mathias Wilhelm & Florian Bassermann & Bernhard Kuster, 2022. "Linking post-translational modifications and protein turnover by site-resolved protein turnover profiling," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Hasan Vatandaslar & Aitor Garzia & Cindy Meyer & Svenja Godbersen & Laura T. L. Brandt & Esther Griesbach & Jeffrey A. Chao & Thomas Tuschl & Markus Stoffel, 2023. "In vivo PAR-CLIP (viP-CLIP) of liver TIAL1 unveils targets regulating cholesterol synthesis and secretion," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    13. Thao Nguyen & Eli J. Costa & Tim Deibert & Jose Reyes & Felix C. Keber & Miroslav Tomschik & Michael Stadlmeier & Meera Gupta & Chirag K. Kumar & Edward R. Cruz & Amanda Amodeo & Jesse C. Gatlin & Mar, 2022. "Differential nuclear import sets the timing of protein access to the embryonic genome," Nature Communications, Nature, vol. 13(1), pages 1-16, 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:13:y:2022:i:1:d:10.1038_s41467-022-35054-2. 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.