A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins

Abstract

Yeast Sfh5 is an unusual member of the Sec14-like phosphatidylinositol transfer protein (PITP) family. Whereas PITPs are defined by their abilities to transfer phosphatidylinositol between membranes in vitro, and to stimulate phosphoinositide signaling in vivo, Sfh5 does not exhibit these activities. Rather, Sfh5 is a redox-active penta-coordinate high spin FeIII hemoprotein with an unusual heme-binding arrangement that involves a co-axial tyrosine/histidine coordination strategy and a complex electronic structure connecting the open shell iron d-orbitals with three aromatic ring systems. That Sfh5 is not a PITP is supported by demonstrations that heme is not a readily exchangeable ligand, and that phosphatidylinositol-exchange activity is resuscitated in heme binding-deficient Sfh5 mutants. The collective data identify Sfh5 as the prototype of a new class of fungal hemoproteins, and emphasize the versatility of the Sec14-fold as scaffold for translating the binding of chemically distinct ligands to the control of diverse sets of cellular activities.

Data availability

Diffraction data have been deposited in PDB under the accession code 6W32.All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

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Author details

  1. Danish Khan

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0650-3990
  2. Dongju Lee

    Department of Molecular and Cellular Medicine, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Gulcin Gulten

    Biochemistry, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Anup Aggarwal

    Biochemistry and Biophysics, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Joshua Wofford

    Chemistry, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Inna Krieger

    Biochemistry and Biophysics, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ashutosh Tripathi

    Department of Molecular and Cellular Medicine, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. John W Patrick

    Chemistry, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Debra M Eckert

    Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Arthur Laganowsky

    Department of Chemistry, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. James Sacchettini

    Biochemistry/Biophysics, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5767-2367
  12. Paul Lindahl

    Chemistry, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Vytas A Bankaitis

    molecular & cellular medicine, Texas A&M University, College Station, United States
    For correspondence
    vytas@tamu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1654-6759

Funding

National Institute of General Medical Sciences (R35 GM131804)

  • Vytas A Bankaitis

Welch Foundation (BE-0017)

  • Vytas A Bankaitis

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

Reviewing Editor

  1. Benoît Kornmann, University of Oxford, United Kingdom

Version history

  1. Received: March 20, 2020
  2. Accepted: August 10, 2020
  3. Accepted Manuscript published: August 11, 2020 (version 1)
  4. Version of Record published: September 1, 2020 (version 2)

Copyright

© 2020, Khan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Danish Khan
  2. Dongju Lee
  3. Gulcin Gulten
  4. Anup Aggarwal
  5. Joshua Wofford
  6. Inna Krieger
  7. Ashutosh Tripathi
  8. John W Patrick
  9. Debra M Eckert
  10. Arthur Laganowsky
  11. James Sacchettini
  12. Paul Lindahl
  13. Vytas A Bankaitis
(2020)
A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins
eLife 9:e57081.
https://doi.org/10.7554/eLife.57081

Share this article

https://doi.org/10.7554/eLife.57081

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