Plant pathogenesis–related proteins of the cacao fungal pathogen Moniliophthora perniciosa differ in their lipid-binding specificities

Darwiche, Rabih; Atab, Ola El; Baroni, Renata Moro; Mondego, Jorge Maurı́cio Costa; Pereira, Gonçalo Amarante Guimarães; Schneiter, Roger

doi:10.1074/jbc.m117.811398

Cited by 20 publications

(30 citation statements)

References 34 publications

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“…The ability to bind and export sterols has been experimentally confirmed for different CAP proteins [ 7 , 9 , 10 ]. Noteworthy, there are also examples of CAP proteins that do not show sterol binding but have evolved other ligand binding specificities [ 8 , 28 ]. As binding and sequestering of host sterols might influence virulence attributes by compromising host cell membrane integrity or signal transduction, we wanted to investigate the ability of Rbe1p and Rbt4p to bind sterols.…”

Section: Resultsmentioning

confidence: 99%

Localization and functional characterization of the pathogenesis-related proteins Rbe1p and Rbt4p in Candida albicans

et al. 2018

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Members of the Cysteine-rich secretory protein, Antigen 5 and Pathogenesis-related 1 (CAP) protein superfamily are important virulence factors in fungi but remain poorly characterized on molecular level. Here, we investigate the cellular localization and molecular function of Rbe1p and Rbt4p, two CAP family members from the human pathogen Candida albicans. We unexpectedly found that Rbe1p localizes to budding sites of yeast cells in a disulfide bond-dependent manner. Furthermore, we show that Rbe1p and Rbt4p bind free cholesterol in vitro and export cholesteryl acetate in vivo. These findings suggest a previously undescribed role for Rbe1p in cell wall-associated processes and a possible connection between the virulence attributes of fungal CAP proteins and sterol binding.

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Section: Resultsmentioning

confidence: 99%

Localization and functional characterization of the pathogenesis-related proteins Rbe1p and Rbt4p in Candida albicans

et al. 2018

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“…A,B). Consistent with this notion, CAP family member from the cacao pathogen Moniliophthora perniciosa that do not bind cholesterol can be converted into sterol binders by a single point mutation in their caveolin‐binding motif . The mode of sterol binding by Pry1 is thus different from that of other cytosolic sterol‐binding proteins such as Osh4, StAR/STARD1, or NPC2, which all bind the lipid in a deep hydrophobic tunnel buried inside the protein .…”

Section: Pathogen‐related In Yeast Pry Proteins Bind and Export Sterolsmentioning

confidence: 97%

The function of yeast CAP family proteins in lipid export, mating, and pathogen defense

et al. 2017

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In their natural habitat, yeast cells are constantly challenged by changing environmental conditions and a fierce competition for limiting resources. To thrive under such conditions, cells need to adapt and divide quickly, and be able to neutralize the toxic compounds secreted by their neighbors. Proteins like the pathogen‐related yeast, Pry proteins, which belong to the large CAP/SCP/TAPS superfamily, may have an important role in this function. CAP proteins are conserved from yeast to man and are characterized by a unique αβα sandwich fold. They are mostly secreted glycoproteins and have been implicated in many different physiological processes including pathogen defense, virulence, venom toxicity, and sperm maturation. Yeast members of this family bind and export sterols as well as fatty acids, and they render cells resistant to eugenol, an antimicrobial compound present in clove oil. CAP family members might thus exert their various physiological functions through binding, sequestration, and neutralization of such small hydrophobic compounds.

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“…Since sterols have important functions in membrane polarization and other aspects of the mating reaction, such as signal transduction, it is plausible that a sterol-binding activity of Pry3 could negatively impact the mating reaction (Aguilar et al, 2010;Jin et al, 2008). Sterol binding by the CAP domain requires a flexible loop rich in aromatic amino acids, termed the caveolin-binding domain, and mutations in this domain abrogate sterol binding both in vivo and in vitro (Choudhary et al, 2014;Darwiche et al, 2017a). To test whether the CAP domain of Pry3 also binds sterols and whether this sterol binding function is important for the observed mating phenotype, we expressed hexahistidine-tagged versions of the CAP domains of Pry1 and Pry3 in Escherichia coli and purified the proteins by affinity chromatography.…”

Section: The Lipid-binding Function Of the Cap Domain Is Not Requiredmentioning

confidence: 99%

“…CAP superfamily members from Saccharomyces cerevisiae, termed pathogen related in yeast (Pry proteins), promote the export of sterols and fatty acids in vivo and purified Pry1 binds these two lipids in distinct non-overlapping binding sites in vitro (Choudhary and Schneiter, 2012;Darwiche et al, 2017b). The fatty acid-and sterol-binding sites are both confined to the conserved CAP domain and CAP family members from other species have also been shown to bind sterols and fatty acids (Darwiche et al, 2016(Darwiche et al, , 2017aGamir et al, 2017;Kelleher et al, 2014). These results indicate that lipid-binding and sequestration may constitute a shared mode of action of CAP family members (Breen et al, 2017;Darwiche et al, 2018;Kazan and Gardiner, 2017).…”

Section: Introductionmentioning

confidence: 99%

The yeast cell wall protein Pry3 inhibits mating through highly conserved residues within the CAP domain

et al. 2020

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Members of the CAP/SCP/TAPS superfamily have been implicated in many different physiological processes, including pathogen defense, sperm maturation and fertilization. The mode of action of this class of proteins, however, remains poorly understood. The genome of Saccharomyces cerevisiae encodes three CAP superfamily members, Pry1-3. We have previously shown that Pry1 function is required for the secretion of sterols and fatty acids. Here, we analyze the function of Pry3, a GPI-anchored cell wall protein. Overexpression of Pry3 results in strong reduction of mating efficiency, providing for a cell-based readout for CAP protein function. Mating inhibition is a conserved function of the CAP domain and depends on highly conserved surface exposed residues that form part of a putative catalytic metal-ion binding site. Pry3 displays polarized cell surface localization adjacent to bud scars, but is absent from mating projections. When overexpressed, however, the protein leaks onto mating projections, suggesting that mating inhibition is due to mislocalization of the protein. Trapping of the CAP domain within the cell wall through a GPI-anchored nanobody results in a dose-dependent inhibition of mating, suggesting that a membrane proximal CAP domain inhibits a key step in the mating reaction, which is possibly related to the function of CAP domain proteins in mammalian fertilization.This article has an associated First Person interview with the first author of the paper.

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Plant pathogenesis–related proteins of the cacao fungal pathogen Moniliophthora perniciosa differ in their lipid-binding specificities

Cited by 20 publications

References 34 publications

Localization and functional characterization of the pathogenesis-related proteins Rbe1p and Rbt4p in Candida albicans

Localization and functional characterization of the pathogenesis-related proteins Rbe1p and Rbt4p in Candida albicans

The function of yeast CAP family proteins in lipid export, mating, and pathogen defense

The yeast cell wall protein Pry3 inhibits mating through highly conserved residues within the CAP domain

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