Two granzyme A/K homologs in Zebra mbuna have different specificities, one classical tryptase and one with chymase activity

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Aybay, ErdemUppsala universitet,Institutionen för cell- och molekylärbiologi (author)

Two granzyme A/K homologs in Zebra mbuna have different specificities, one classical tryptase and one with chymase activity

Article/chapterEnglish2023

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Elsevier,2023
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-514069
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-514069URI
https://doi.org/10.1016/j.dci.2023.104920DOI
https://res.slu.se/id/publ/126351URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTLs) and natural killer (NK) cells. The locus encoding these two proteases is the first of the hematopoietic serine protease loci to appear during vertebrate evolution. This locus is found in all jawed vertebrates including the cartilaginous fishes. Granzyme A is the most abundant of the different granzymes expressed by CTLs and NK cells and its potential function has been studied extensively for many years. However, no clear conclusions concerning its primary role in the immune defense has been obtained. In all mammals, there are only one copy each of granzyme A and K, whereas additional copies are found in both cartilaginous and ray finned fishes. In cichlids two of these copies seem to encode new members of the granzyme A/K family. These two new members appear to have changed primary specificity and to be pure chymases based on the amino acids in their active site substrate binding pockets. Interestingly, one of these gene copies is located in the middle of the granzyme A/K locus, while the other copy is present in another locus, the met-ase locus. We here present a detailed characterization of the extended cleavage specificity of one of these non-classical granzymes, a Zebra mbuna granzyme positioned in the granzyme A/K locus. This enzyme, named granzyme A2, showed a high preference for tyrosine in the P1 position of substrates, thereby being a strict chymase. We have also characterized one of the classical granzyme A/Ks of the Zebra mbuna, granzyme A1, which is a tryptase with preference for arginine in the P1 position of substrates. Based on their extended specificities, the two granzymes showed major similarities, but also some differences in preferred amino acids in positions surrounding the cleavable amino acid. Fish lack one of the hematopoietic serine protease loci of mammals, the chymase locus, where one of the major mast cell enzymes is located. An interesting question is now if cichlids have by compensatory mechanisms generated a mast cell chymase from another locus, and if similar chymotryptic enzymes have appeared also in other fish species.

Subject headings and genre

NATURVETENSKAP Biologi Immunologi hsv//swe
NATURAL SCIENCES Biological Sciences Immunology hsv//eng
NATURVETENSKAP Biologi Biokemi och molekylärbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Biochemistry and Molecular Biology hsv//eng
LANTBRUKSVETENSKAPER Lantbruksvetenskap, skogsbruk och fiske Fisk- och akvakulturforskning hsv//swe
AGRICULTURAL SCIENCES Agriculture, Forestry and Fisheries Fish and Aquacultural Science hsv//eng
Cytotoxic T cells
NK cell
Granzyme A
Apoptosis
Caspase
Chymase

Added entries (persons, corporate bodies, meetings, titles ...)

Elkhalifa, MamounUppsala universitet,Institutionen för cell- och molekylärbiologi (author)
Akula, SrinivasSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Mikrobiologi och immunologi,Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Box 7011, SE-75007 Uppsala, Sweden.,Institutionen för anatomi, fysiologi och biokemi (AFB),Department of Anatomy, Physiology and Biochemistry (AFB),Uppsala University(Swepub:uu)akusr139 (author)
Wernersson, SaraSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för anatomi, fysiologi och biokemi (AFB),Department of Anatomy, Physiology and Biochemistry (AFB),Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Box 7011, SE-75007 Uppsala, Sweden.(Swepub:slu)48577 (author)
Hellman, LarsUppsala universitet,Mikrobiologi och immunologi(Swepub:uu)larshell (author)
Uppsala universitetInstitutionen för cell- och molekylärbiologi (creator_code:org_t)
Sveriges lantbruksuniversitet

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In:Developmental and Comparative Immunology: Elsevier1480145-305X1879-0089

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By the author/editor: Aybay, Erdem; Elkhalifa, Mamou ...; Akula, Srinivas; Wernersson, Sara; Hellman, Lars

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NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Immunology

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

AGRICULTURAL SCIENCES: AGRICULTURAL SCI ...; and Agriculture Fore ...; and Fish and Aquacul ...

Articles in the publication: Developmental an ...

By the university: Uppsala University; Swedish University of Agricultural Sciences

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