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Cocaprins, β-Trefoil Fold Inhibitors of Cysteine and Aspartic Proteases from Coprinopsis cinerea

Summary

Scientists discovered new proteins called cocaprins from mushrooms that can block different types of protein-cutting enzymes. This research helps us understand how fungi protect themselves and regulate their own biological processes. Impact on everyday life: – Could lead to development of new enzyme-blocking drugs – Provides insights into fungal defense mechanisms – Advances our understanding of protein structure and function – May help develop new strategies for crop protection – Could inspire new biotechnology applications

Background

Protease inhibitors are important regulators of proteolytic activity involved in many physiological and pathological processes. Fungal protease inhibitors show great versatility, including unique inhibitory mechanisms. The β-trefoil fold protease inhibitors are well characterized and consist of 12 β-strands folded into structurally similar units with pseudo-3-fold symmetry.

Objective

To characterize a new family of fungal protease inhibitors called cocaprins from Coprinopsis cinerea that can inhibit both cysteine and aspartic proteases, and determine their structure and biological functions.

Results

Two cocaprin-encoding genes showed differential expression in fungal tissues – one highly expressed in vegetative mycelium and the other in fruiting body stipes. The proteins (15 kDa) formed dimers and had acidic isoelectric points. The crystal structure revealed similarity to fungal β-trefoil lectins. Cocaprins inhibited plant C1 family cysteine proteases and pepsin with Ki values in the micromolar range. Mutagenesis showed different inhibitory sites for aspartic and cysteine proteases. The proteins also showed weak potential for glycan binding.

Conclusion

Cocaprins represent a new family of dual-headed protease inhibitors that can target both cysteine and aspartic proteases through different inhibitory sites. They are the first characterized aspartic protease inhibitors with β-trefoil fold from fungi, demonstrating the remarkable plasticity of loop functionalization in fungal β-trefoil proteins. Their biological role appears to involve regulation of endogenous proteolytic activities or defense against fungal antagonists.
  • Published in:International Journal of Molecular Sciences,
  • Study Type:Basic Research,
  • Source: 10.3390/ijms23094916
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