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Article

Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion

1
Institute of Parasitology, Biology Centre, Academy of Sciences of the Czech Republic, Branišovská 1160/31, 37005 České Budějovice, Czech Republic
2
Department of Medical Biology, Faculty of Science, University of South Bohemia in České Budějovice, Branišovská 1760c, 37005 České Budějovice, Czech Republic
3
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo n. 2, 16610 Praha, Czech Republic
4
Department of Biochemistry, Faculty of Science, Charles University, Hlavova 2030/8, 12800 Prague, Czech Republic
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrea Battistoni
Int. J. Mol. Sci. 2021, 22(10), 5371; https://doi.org/10.3390/ijms22105371
Received: 18 April 2021 / Revised: 13 May 2021 / Accepted: 17 May 2021 / Published: 20 May 2021
(This article belongs to the Special Issue Molecular Biology of Disease Vectors)
The hard tick Ixodes ricinus is a vector of Lyme disease and tick-borne encephalitis. Host blood protein digestion, essential for tick development and reproduction, occurs in tick midgut digestive cells driven by cathepsin proteases. Little is known about the regulation of the digestive proteolytic machinery of I. ricinus. Here we characterize a novel cystatin-type protease inhibitor, mialostatin, from the I. ricinus midgut. Blood feeding rapidly induced mialostatin expression in the gut, which continued after tick detachment. Recombinant mialostatin inhibited a number of I. ricinus digestive cysteine cathepsins, with the greatest potency observed against cathepsin L isoforms, with which it co-localized in midgut digestive cells. The crystal structure of mialostatin was determined at 1.55 Å to explain its unique inhibitory specificity. Finally, mialostatin effectively blocked in vitro proteolysis of blood proteins by midgut cysteine cathepsins. Mialostatin is likely to be involved in the regulation of gut-associated proteolytic pathways, making midgut cystatins promising targets for tick control strategies. View Full-Text
Keywords: cathepsin; crystal structure; cysteine protease; digestion; Ixodes ricinus; midgut; parasite cathepsin; crystal structure; cysteine protease; digestion; Ixodes ricinus; midgut; parasite
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MDPI and ACS Style

Kotál, J.; Buša, M.; Urbanová, V.; Řezáčová, P.; Chmelař, J.; Langhansová, H.; Sojka, D.; Mareš, M.; Kotsyfakis, M. Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion. Int. J. Mol. Sci. 2021, 22, 5371. https://doi.org/10.3390/ijms22105371

AMA Style

Kotál J, Buša M, Urbanová V, Řezáčová P, Chmelař J, Langhansová H, Sojka D, Mareš M, Kotsyfakis M. Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion. International Journal of Molecular Sciences. 2021; 22(10):5371. https://doi.org/10.3390/ijms22105371

Chicago/Turabian Style

Kotál, Jan, Michal Buša, Veronika Urbanová, Pavlína Řezáčová, Jindřich Chmelař, Helena Langhansová, Daniel Sojka, Michael Mareš, and Michail Kotsyfakis. 2021. "Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion" International Journal of Molecular Sciences 22, no. 10: 5371. https://doi.org/10.3390/ijms22105371

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