Počet záznamů: 1
Characterization of Gut-associated Cathepsin D Hemoglobinase from Tick Ixodes ricinus (IrCD1)
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SYSNO ASEP 0377766 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Characterization of Gut-associated Cathepsin D Hemoglobinase from Tick Ixodes ricinus (IrCD1) Tvůrce(i) Sojka, Daniel (BC-A) RID, ORCID
Franta, Zdeněk (BC-A)
Frantová, Helena (BC-A) ORCID
Bartošová, Pavla (BC-A) RID, ORCID
Horn, Martin (UOCHB-X) RID, ORCID
Váchová, Jana (UOCHB-X)
O’Donoghue, A. J. (US)
Eroy-Reveles, A. A. (US)
Craik, C. S. (US)
Knudsen, G. M. (US)
Caffrey, C. R. (US)
McKerrow, J. H. (US)
Mareš, Michael (UOCHB-X) RID, ORCID
Kopáček, Petr (BC-A) RID, ORCIDZdroj.dok. Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 287, č. 25 (2012), s. 21152-21163Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova RHIPICEPHALUS BOOPHILUS MICROPLUS ; HARD TICK ; ORNITHODOROS-MOUBATA ; ASPARTIC PROTEINASE ; RECOGNITION DOMAIN ; MOLECULAR-CLONING ; ACTIVE-SITE ; EXPRESSION ; INHIBITOR ; PROTEASE Vědní obor RIV EB - Genetika a molekulární biologie CEP IAA600960910 GA AV ČR - Akademie věd LC06009 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy KJB600960911 GA AV ČR - Akademie věd GPP502/11/P682 GA ČR - Grantová agentura ČR IAA400550705 GA AV ČR - Akademie věd GAP207/10/2183 GA ČR - Grantová agentura ČR Institucionální podpora UOCHB-X - RVO:61388963 CEZ AV0Z60220518 - PAU-O, BC-A (2005-2011) UT WOS 000306416800036 DOI 10.1074/jbc.M112.347922 Anotace To identify the gut-associated tick aspartic hemoglobinase, this work focuses on the functional diversity of multiple Ixodes ricinus cathepsin D forms (IrCDs). Out of three encoding genes representing Ixodes scapularis genome paralogs, IrCD1 is the most distinct enzyme with a shortened propeptide region and a unique pattern of predicted post-translational modifications. IrCD1 gene transcription is induced by tick feeding and is restricted to the gut tissue. The hemoglobinolytic role of IrCD1 was further supported by immunolocalization of IrCD1 in the vesicles of tick gut cells. Properties of recombinantly expressed rIrCD1 are consistent with the endo-lysosomal environment because the zymogen is autoactivated and remains optimally active in acidic conditions. Hemoglobin cleavage pattern of rIrCD1 is identical to that produced by the native enzyme. The preference for hydrophobic residues at the P1 and P1' position was confirmed by screening a novel synthetic tetradecapeptidyl substrate library. Outside the S1-S1' regions, rIrCD1 tolerates most amino acids but displays a preference for tyrosine at P3 and alanine at P2'. Further analysis of the cleavage site location within the peptide substrate indicated that IrCD1 is a true endopeptidase. The role in hemoglobinolysis was verified with RNAi knockdown of IrCD1 that decreased gut extract cathepsin D activity by >90%. IrCD1 was newly characterized as a unique hemoglobinolytic cathepsin D contributing to the complex intestinal proteolytic network of mainly cysteine peptidases in ticks. Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2013
Počet záznamů: 1