Discovery of fungal surface NADases predominantly present in pathogenic species

DOI: 10.1038/s41467-021-21307-z

Authors: Oyvind Stromland (University of Bergen) , Juha P. Kallio (University of Bergen) , Annica Pschibul (Hans Knöll Institute) , Renate H. Skoge (University of Bergen) , Hulda M. Harðardóttir (University of Bergen) , Lars J. Sverkeli (University of Bergen) , Thorsten Heinekamp (Hans Knöll Institute) , Olaf Kniemeyer (Hans Knöll Institute) , Marie Migaud (University of South Alabama) , Mikhail V. Makarov (University of South Alabama) , Toni I. Gossmann (Bielefeld University; University of Sheffield) , Axel A. Brakhage (Hans Knöll Institute; Friedrich Schiller University Jena) , Mathias Ziegler (University of Bergen)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 12

State: Published (Approved)
Published: March 2021

Abstract: Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host’s NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.

Journal Keywords: Fungal biology; Hydrolases; Pathogens; X-ray crystallography

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I04-Macromolecular Crystallography

Other Facilities: P11 and P13 at PETRA III

Documents:
s41467-021-21307-z.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Drug Discovery Pathogens Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)