A fungal family of lytic polysaccharide monooxygenase-like copper proteins

Labourel, Aurore; Frandsen, Kristian E. H.; Zhang, Feng; Brouilly, Nicolas; Grisel, Sacha; Haon, Mireille; Ciano, Luisa; Ropartz, David; Fanuel, Mathieu; Martin, Francis; Navarro, David; Rosso, Marie‐Noëlle; Tandrup, Tobias; Bissaro, Bastien; Johansen, Katja Salomon; Zerva, Anastasia; Walton, Paul H.; Henrissat, Bernard; Leggio, Leila Lo; Berrin, Jean‐Guy

doi:10.1038/s41589-019-0438-8

Cited by 66 publications

(73 citation statements)

References 63 publications

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“…While in vitro studies show that the amino-terminal peptide of human Ctr1 can collect Cu 2+ from albumin 40 , ceruloplasmin can provide Cu to both Ctr1-dependent and Ctr1-independent Cu uptake mechanisms in cultured cells 39 . Additionally, some forms of CopC, a periplasmic protein found in bacteria, bind a single Cu 2+ atom using His and Asp ligands 18 similar to that identified in the La X325 protein 32 and conserved in Bim1. Indirect evidence suggests that CopC could function in an analogous fashion to Bim1-Ctr1, in concert with the inner membrane protein CopD to import Cu 18 , 41 .…”

Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

“…Bim1 shows high sequence homology (36% identity) to novel GPI-anchored LPMO-like proteins from the fungi Laetisaria arvalis and Laccaria bicolor 32 . Given the conservation with these proteins of the Cu 2+ -coordinating histidines and a GPI anchor, a structural model for Bim1 was generated based on the La X325 structure 32 ( Figure 4a , Supplementary Table 2 ). The threaded structural model of Bim1 displays the putative histidine brace Cu 2+ - coordinating ligands found in all LPMOs (H20 and H65) and a potential aspartic acid Cu 2+ ligand (D138) found within a glycine-rich loop of La X325 ( Figure 4b ).…”

Section: Resultsmentioning

confidence: 99%

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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

et al. 2020

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Infection by the fungal pathogen Cryptococcus neoformans causes lethal meningitis, primarily in immune-compromised individuals. Colonization of the brain by C. neoformans is dependent on copper (Cu) acquisition from the host, which drives critical virulence mechanisms. While C. neoformans Cu + import and virulence are dependent on the Ctr1 and Ctr4 proteins, little is known concerning extracellular Cu ligands that participate in this process. We identified a C. neoformans gene, BIM1 , strongly induced during Cu limitation and which encodes a protein related to Lytic Polysaccharide Monooxygenases (LPMOs). Surprisingly, bim1 mutants are Cu deficient and Bim1 function in Cu accumulation depends upon Cu 2+ coordination and cell surface association via a GPI anchor. Bim1 participates in Cu uptake in concert with Ctr1 and expression of this pathway drives brain colonization in mouse infection models. These studies demonstrate a new role for LPMO-like proteins as a critical factor for Cu acquisition in fungal meningitis.

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Section: Discussionmentioning

confidence: 95%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

et al. 2020

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“…This is in agreement with the very limited reduction of Cu(II)-Bim1 during EXAFS analysis 5 . Also, the Cu-coordination geometry in the crystal structures of the structurally related protein LaX325 is consistent with Cu(II), and thus with no photoreduction of the metal by the X-rays during collection of the diffraction data 6 . The apparent acceleration of ascorbate oxidation by Cu(II)-Bim1 is instead caused by un-ligated copper being released from the histidine brace.…”

Section: Discussionmentioning

confidence: 62%

“…The C-terminal His tag was removed from the protein using TEV protease. The structure of LaX325 has recently been determined by X-ray crystallography 6 and the structure of Bim1 (36% identical in sequence) was modelled on this basis (Fig. 2) 5 .…”

Section: Results Preparation Copper Binding and Structural Analysis mentioning

confidence: 99%

Biochemical evidence of both copper chelation and oxygenase activity at the histidine brace

Brander

Horváth

Ipsen

et al. 2020

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Lytic polysaccharide monooxygenase (LPMO) and copper binding protein CopC share a similar mononuclear copper site. This site is defined by an N-terminal histidine and a second internal histidine side chain in a configuration called the histidine brace. To understand better the determinants of reactivity, the biochemical and structural properties of a well-described cellulose-specific LPMO from Thermoascus aurantiacus (TaAA9A) is compared with that of CopC from Pseudomonas fluorescens (PfCopC) and with the LPMO-like protein Bim1 from Cryptococcus neoformans. PfCopC is not reduced by ascorbate but is a very strong Cu(II) chelator due to residues that interacts with the N-terminus. This first biochemical characterization of Bim1 shows that it is not redox active, but very sensitive to H2O2, which accelerates the release of Cu ions from the protein. TaAA9A oxidizes ascorbate at a rate similar to free copper but through a mechanism that produce fewer reactive oxygen species. These three biologically relevant examples emphasize the diversity in how the proteinaceous environment control reactivity of Cu with O2.

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Copper binding and reactivity at the histidine brace motif: insights from mutational analysis of the Pseudomonas fluorescens copper chaperone CopC

et al. 2021

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The histidine brace (His-brace) is a copper-binding motif that is associated with both oxidative enzymes and proteinaceous copper chaperones. Here, we used biochemical and structural methods to characterize mutants of a Hisbrace-containing copper chaperone from Pseudomonas fluorescens (PfCopC). A total of 15 amino acid variants in primary and second-sphere residues were produced and characterized in terms of their copper binding and redox properties. PfCopC has a very high affinity for Cu(II) and also binds Cu(I). A high reorganization barrier likely prevents redox cycling and, thus, catalysis. In contrast, mutations in the conserved second-sphere Glu27 enable slow oxidation of ascorbate. The crystal structure of the variant E27A confirmed copper binding at the His-brace. Unexpectedly, Asp83 at the equatorial position was shown to be indispensable for Cu(II) binding in the His-brace of PfCopC. A PfCopC mutant that was designed to mimic the His-brace from lytic polysaccharide monooxygenase-like family X325 did not bind Cu(II), but was still able to bind Cu(I). These results highlight the importance of the proteinaceous environment around the copper His-brace for reactivity and, thus, the difference between enzyme and chaperone.

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A fungal family of lytic polysaccharide monooxygenase-like copper proteins

Cited by 66 publications

References 63 publications

A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

A lytic polysaccharide monooxygenase-like protein functions in fungal copper import and meningitis

Biochemical evidence of both copper chelation and oxygenase activity at the histidine brace

Copper binding and reactivity at the histidine brace motif: insights from mutational analysis of the Pseudomonas fluorescens copper chaperone CopC

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