Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00580493" target="_blank" >RIV/60077344:_____/23:00580493 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/23:00580493 RIV/60076658:12310/23:43906690
Result on the web
<a href="https://link.springer.com/article/10.1007/s00018-023-04993-4" target="_blank" >https://link.springer.com/article/10.1007/s00018-023-04993-4</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00018-023-04993-4" target="_blank" >10.1007/s00018-023-04993-4</a>
Alternative languages
Result language
angličtina
Original language name
Protease-bound structure of Ricistatin provides insights into the mechanism of action of tick salivary cystatins in the vertebrate host
Original language description
Tick saliva injected into the vertebrate host contains bioactive anti-proteolytic proteins from the cystatin family, however, the molecular basis of their unusual biochemical and physiological properties, distinct from those of host homologs, is unknown. Here, we present Ricistatin, a novel secreted cystatin identified in the salivary gland transcriptome of Ixodes ricinus ticks. Recombinant Ricistatin inhibited host-derived cysteine cathepsins and preferentially targeted endopeptidases, while having only limited impact on proteolysis driven by exopeptidases. Determination of the crystal structure of Ricistatin in complex with a cysteine cathepsin together with characterization of structural determinants in the Ricistatin binding site explained its restricted specificity. Furthermore, Ricistatin was potently immunosuppressive and anti-inflammatory, reducing levels of pro-inflammatory cytokines IL-6, IL-1 beta, and TNF-alpha and nitric oxide in macrophages, IL-2 and IL-9 levels in Th9 cells, and OVA antigen-induced CD4(+) T cell proliferation and neutrophil migration. This work highlights the immunotherapeutic potential of Ricistatin and, for the first time, provides structural insights into the unique narrow selectivity of tick salivary cystatins determining their bioactivity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular and Molecular Life Sciences
ISSN
1420-682X
e-ISSN
1420-9071
Volume of the periodical
80
Issue of the periodical within the volume
11
Country of publishing house
CH - SWITZERLAND
Number of pages
17
Pages from-to
339
UT code for WoS article
001093315500001
EID of the result in the Scopus database
2-s2.0-85174918368