Periprotein lipidomes of Saccharomyces cerevisiae provide a flexible environment for conformational changes of membrane proteins

  1. Joury S van 't Klooster
  2. Tan-Yun Cheng
  3. Hendrik R Sikkema
  4. Aike Jeucken
  5. Branch Moody
  6. Bert Poolman  Is a corresponding author
  1. University of Groningen, Netherlands
  2. Harvard Medical School, United States

Abstract

Yeast tolerates a low pH and high solvent concentrations. The permeability of the plasma membrane (PM) for small molecules is low and lateral diffusion of proteins is slow. These findings suggest a high degree of lipid order, which raises the question of how membrane proteins function in such an environment. The yeast PM is segregated into the Micro-Compartment-of-Can1 (MCC) and Pma1 (MCP), which have different lipid compositions. We extracted proteins from these microdomains via stoichiometric capture of lipids and proteins in styrene-maleic-acid-lipid-particles (SMALPs). We purified SMALP-lipid-protein complexes by chromatography and quantitatively analyzed periprotein lipids located within the diameter defined by one SMALP. Phospholipid and sterol concentrations are similar for MCC and MCP, but sphingolipids are enriched in MCP. Ergosterol is depleted from this periprotein lipidome, whereas phosphatidylserine is enriched relative to the bulk of the plasma membrane. Direct detection of PM lipids in the 'periprotein space' supports the conclusion that proteins function in the presence of a locally disordered lipid state.

Data availability

All data generated or analyses are included in the manuscript and supporting files.

Article and author information

Author details

  1. Joury S van 't Klooster

    Department of Biochemistry, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  2. Tan-Yun Cheng

    Division of Rheumatology, Inflammation and Immunity, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5178-6985
  3. Hendrik R Sikkema

    Department of Biochemistry, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Aike Jeucken

    Department of Biochemistry, University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Branch Moody

    Division of Rheumatology, Inflammation and Immunity, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Bert Poolman

    Department of Biochemistry, University of Groningen, Groningen, Netherlands
    For correspondence
    b.poolman@rug.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1455-531X

Funding

Ministry of Economic Affairs, The Netherlands (BE-BASIC)

  • Bert Poolman

European Research Council (ERC Advanced #670578)

  • Bert Poolman

NIH (AR048632)

  • Branch Moody

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Version history

  1. Received: March 17, 2020
  2. Accepted: April 9, 2020
  3. Accepted Manuscript published: April 17, 2020 (version 1)
  4. Version of Record published: April 24, 2020 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,232
    Page views
  • 354
    Downloads
  • 35
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Joury S van 't Klooster
  2. Tan-Yun Cheng
  3. Hendrik R Sikkema
  4. Aike Jeucken
  5. Branch Moody
  6. Bert Poolman
(2020)
Periprotein lipidomes of Saccharomyces cerevisiae provide a flexible environment for conformational changes of membrane proteins
eLife 9:e57003.
https://doi.org/10.7554/eLife.57003

Share this article

https://doi.org/10.7554/eLife.57003

Further reading

    1. Biochemistry and Chemical Biology
    2. Cell Biology
    Chenjie Xia, Huihui Xu ... Hongting Jin
    Research Article

    Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased β-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting β-catenin signaling in glucocorticoid-induced GONFH rats. Col2+ lineage largely contributes to BMSCs and was found an osteogenic commitment in the femoral head through 9 mo of lineage trace. Specific deletion of β-catenin gene (Ctnnb1) in Col2+ cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that β-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH and identify an ideal genetic-modified mouse model of GONFH.

    1. Biochemistry and Chemical Biology
    2. Plant Biology
    Pradeep Kumar, Ankit Roy ... Rajan Sankaranarayanan
    Research Article

    Aldehydes, being an integral part of carbon metabolism, energy generation, and signalling pathways, are ingrained in plant physiology. Land plants have developed intricate metabolic pathways which involve production of reactive aldehydes and its detoxification to survive harsh terrestrial environments. Here, we show that physiologically produced aldehydes, i.e., formaldehyde and methylglyoxal in addition to acetaldehyde, generate adducts with aminoacyl-tRNAs, a substrate for protein synthesis. Plants are unique in possessing two distinct chiral proofreading systems, D-aminoacyl-tRNA deacylase1 (DTD1) and DTD2, of bacterial and archaeal origins, respectively. Extensive biochemical analysis revealed that only archaeal DTD2 can remove the stable D-aminoacyl adducts on tRNA thereby shielding archaea and plants from these system-generated aldehydes. Using Arabidopsis as a model system, we have shown that the loss of DTD2 gene renders plants susceptible to these toxic aldehydes as they generate stable alkyl modification on D-aminoacyl-tRNAs, which are recycled only by DTD2. Bioinformatic analysis identifies the expansion of aldehyde metabolising repertoire in land plant ancestors which strongly correlates with the recruitment of archaeal DTD2. Finally, we demonstrate that the overexpression of DTD2 offers better protection against aldehydes than in wild type Arabidopsis highlighting its role as a multi-aldehyde detoxifier that can be explored as a transgenic crop development strategy.