Cospin is a

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...

inhibitor from the

mushroom A mushroom or toadstool is the fleshy, spore-bearing fruiting body of a fungus, typically produced above ground, on soil, or on its food source. ''Toadstool'' generally denotes one poisonous to humans. The standard for the name "mushroom" is t ...

species ''

Coprinopsis cinerea ''Coprinopsis cinerea'' is a species of mushroom in the family Psathyrellaceae. Commonly known as the gray shag, it is edible, but must be used promptly after collecting. ''Coprinopsis cinerea'' is an important model organism for studying fun ...

'' in the phylum

Basidiomycota Basidiomycota () is one of two large divisions that, together with the Ascomycota, constitute the subkingdom Dikarya (often referred to as the "higher fungi") within the kingdom Fungi. Members are known as basidiomycetes. More specifically, Basi ...

Cospin IC1

It has similar biochemical properties to other well characterized

fungal A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from th ...

serine protease inhibitors of family I66 in the MEROPS classification.Odani S., Tominaga K., Kondou S., Hori H., Koide T., Hara S., Isemura M., Tsunasawa S. (1999) The inhibitory properties and primary structure of a novel serine proteinase inhibitor from the fruiting body of the basidiomycete, Lentinus edodes. Eur. J. Biochem. 262, 915–923

PubMed PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...

Cospin is one of the few serine protease inhibitors of basidiomycete that have been isolated and characterized.Sabotic J., Trcek T., Popovic T., Brzin J. (2007) Basidiomycetes harbor a hidden treasure of proteolytic diversity. J. Biotechnol. 128, 297–307

It is highly expressed in sexual reproductive structures termed fruiting bodies and has been cloned and characterized at the molecular and functional levels.

Genetic background

The cospin PIC 1 gene sequence isolated from fruiting bodies of the C. cinerea strain AmutBmut can be found under GenBank TM accession number ACX48485.Sabotič J, Bleuler-Martinez S, Renko M, et al. Structural Basis of Trypsin Inhibition and Entomotoxicity of Cospin, Serine Protease Inhibitor Involved in Defense of Coprinopsis cinerea Fruiting Bodies. The Journal of Biological Chemistry. 2012;287(6):3898-3907.

Biochemical properties

Cospin is a small

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

and a highly specific trypsin inhibitor. pH stability Recombinant purified Cospin has been found to remain active after incubation in acidic pH 3 and

alkaline In chemistry, an alkali (; from ar, القلوي, al-qaly, lit=ashes of the saltwort) is a base (chemistry), basic, ionic compound, ionic salt (chemistry), salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as ...

pH 11 conditions.

Crystal structure In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystal, crystalline material. Ordered structures occur from the intrinsic nature of the constituent particles to form symmetric pat ...

Cospin is based on a β-trefoil fold. The cospin fold resembles a tree-like structure with 2 loops in the root region, a stem comprising a six-stranded β-barrel, and two layers of loops in the crown region. Cospin, is the first fungal trypsin inhibitor with a determined 3D structure, it utilizes a different loop for trypsin inhibition compared to other beta-trefoil inhibitors.Sasakawa H., Yoshinaga S., Kojima S., Tamura A. (2002): Structure of POIA1, a homologous protein to the propeptide of subtilisin. Implication for protein foldability and the function as an intramolecular chaperone. J. Mol. Biol. 317, 159–167. Substrate binding“cospin is a classic inhibitor that binds to the active site in a substrate-like manner and forms a tight and stable complex with trypsin.” Cospin biotoxicity is not lethal to amoeba A.castellanii,

nematode The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-Parasitism, parasitic nematodes also known as eelworms. They are a diverse animal phylum inhab ...

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...

, and two true fly species. The toxicity caused developmental delay in both

pupae A pupa ( la, pupa, "doll"; plural: ''pupae'') is the life stage of some insects undergoing transformation between immature and mature stages. Insects that go through a pupal stage are holometabolous: they go through four distinct stages in their ...

and flies.

Application

Cospin plays a defensive role against

predator Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill th ...

s and parasites. Cospin toxicity targets specifically fruit fly

D. melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly" or "pomace fly". Starting with Ch ...

. Cospin represents one type of fungal protein mediated defence against

fungivorous Fungivory or mycophagy is the process of organisms consuming fungi. Many different organisms have been recorded to gain their energy from consuming fungi, including birds, mammals, insects, plants, amoebas, gastropods, nematodes, bacteria and othe ...

insects. Cospin a serine protease inhibitor can be of use in various applications ranging from pest management, crop protection to drug development, design for

therapeutics A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...

, and basic medical research.

References

{{reflist Serine protease inhibitors Coprinopsis