8R6T
NMR solution structure of thyropin IrThy-Cd from the hard tick Ixodes ricinus
Summary for 8R6T
| Entry DOI | 10.2210/pdb8r6t/pdb |
| NMR Information | BMRB: 34883 |
| Descriptor | Putative two thyropin protein (Fragment) (1 entity in total) |
| Functional Keywords | structure from cyana 3.98.13, protein binding |
| Biological source | Ixodes ricinus (castor bean tick) |
| Total number of polymer chains | 1 |
| Total formula weight | 7849.62 |
| Authors | Srb, P.,Veverka, V.,Matouskova, Z.,Orsaghova, K.,Mares, M. (deposition date: 2023-11-23, release date: 2024-02-28, Last modification date: 2024-10-09) |
| Primary citation | Matouskova, Z.,Orsaghova, K.,Srb, P.,Pytelkova, J.,Kukacka, Z.,Busa, M.,Hajdusek, O.,Sima, R.,Fabry, M.,Novak, P.,Horn, M.,Kopacek, P.,Mares, M. An Unusual Two-Domain Thyropin from Tick Saliva: NMR Solution Structure and Highly Selective Inhibition of Cysteine Cathepsins Modulated by Glycosaminoglycans. Int J Mol Sci, 25:-, 2024 Cited by PubMed Abstract: The structure and biochemical properties of protease inhibitors from the thyropin family are poorly understood in parasites and pathogens. Here, we introduce a novel family member, Ir-thyropin (IrThy), which is secreted in the saliva of ticks, vectors of Lyme borreliosis and tick-borne encephalitis. The IrThy molecule consists of two consecutive thyroglobulin type-1 (Tg1) domains with an unusual disulfide pattern. Recombinant IrThy was found to inhibit human host-derived cathepsin proteases with a high specificity for cathepsins V, K, and L among a wide range of screened cathepsins exhibiting diverse endo- and exopeptidase activities. Both Tg1 domains displayed inhibitory activities, but with distinct specificity profiles. We determined the spatial structure of one of the Tg1 domains by solution NMR spectroscopy and described its reactive center to elucidate the unique inhibitory specificity. Furthermore, we found that the inhibitory potency of IrThy was modulated in a complex manner by various glycosaminoglycans from host tissues. IrThy was additionally regulated by pH and proteolytic degradation. This study provides a comprehensive structure-function characterization of IrThy-the first investigated thyropin of parasite origin-and suggests its potential role in host-parasite interactions at the tick bite site. PubMed: 38396918DOI: 10.3390/ijms25042240 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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