A Sec14-like phosphatidylinositol transfer protein paralog defines a novel class of heme-binding proteins
- Texas A&M University, United States
- University of Utah School of Medicine, United States
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.
Article and author information
Author details
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
- Benoît Kornmann, University of Oxford, United Kingdom
Version history
- Received: March 20, 2020
- Accepted: August 10, 2020
- Accepted Manuscript published: August 11, 2020 (version 1)
- 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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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
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