A fungal substrate mimicking molecule suppresses plant immunity via an inter-kingdom conserved motif

• Published in: Nature communications Vol. 10; no. 1; p. 1576
• Main Authors: Misas Villamil, Johana C., Mueller, André N., Demir, Fatih, Meyer, Ute, Ökmen, Bilal, Schulze Hüynck, Jan, Breuer, Marlen, Dauben, Helen, Win, Joe, Huesgen, Pitter F., Doehlemann, Gunther
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.04.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 631/326/193/2545; 631/449/2169/2673; 82/58; 82/83; Amino Acid Motifs; Amino acids; Bacteria; Cell cycle; Conserved sequence; Corn; Corn smut; Enzymes; Food supply; Fungal Proteins - chemistry; Fungal Proteins - physiology; Fungi; Genetic engineering; Humanities and Social Sciences; Immunity; Infections; Inhibitors; Mass spectrometry; Mass spectroscopy; Microorganisms; Mimicry; Models, Molecular; multidisciplinary; Papain; Pathogens; Peptides; Plant diseases; Plant immunity; Plant Tumors - microbiology; Proteins; Research parks; Science; Science (multidisciplinary); Substrates; Ustilago - enzymology; Ustilago maydis; Virulence; Virulence Factors - chemistry; Virulence Factors - physiology; Zea mays - immunology; Zea mays - microbiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09472-8

Ustilago maydis is a biotrophic fungus causing corn smut disease in maize. The secreted effector protein Pit2 is an inhibitor of papain-like cysteine proteases (PLCPs) essential for virulence. Pit2 inhibitory function relies on a conserved 14 amino acids motif (PID14). Here we show that synthetic PID14 peptides act more efficiently as PLCP inhibitors than the full-length Pit2 effector. Mass spectrometry shows processing of Pit2 by maize PLCPs, which releases an inhibitory core motif from the PID14 sequence. Mutational analysis demonstrates that two conserved residues are essential for Pit2 function. We propose that the Pit2 effector functions as a substrate mimicking molecule: Pit2 is a suitable substrate for apoplastic PLCPs and its processing releases the embedded inhibitor peptide, which in turn blocks PLCPs to modulate host immunity. Remarkably, the PID14 core motif is present in several plant associated fungi and bacteria, indicating the existence of a conserved microbial inhibitor of proteases (cMIP). Pit2 is a secreted Ustilago maydis effector that contributes to corn smut disease by inhibiting papain-like cysteine proteases (PLCPs) in maize. Here Misas Villamil et al. show that Pit2 mimics PLCP substrates, and is cleaved to release a peptide that blocks PLCP activity and represses host immunity.