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6ztk

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Crystal structure of Mialostatin, a gut cystatin from the hard tick Ixodes ricinus

Structural highlights

6ztk is a 2 chain structure with sequence from Ixodes ricinus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.55Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

V5H924_IXORI

Publication Abstract from PubMed

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 A 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.

Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion.,Kotal J, Busa M, Urbanova V, Rezacova P, Chmelar J, Langhansova H, Sojka D, Mares M, Kotsyfakis M Int J Mol Sci. 2021 May 20;22(10). pii: ijms22105371. doi: 10.3390/ijms22105371. PMID:34065290^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kotal J, Busa M, Urbanova V, Rezacova P, Chmelar J, Langhansova H, Sojka D, Mares 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 May 20;22(10). pii: ijms22105371. doi: 10.3390/ijms22105371. PMID:34065290 doi:http://dx.doi.org/10.3390/ijms22105371