An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure.
Ra-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI proteins. We report the detection, purification and characterization of the function of Ra-KLP. In addition, determination of the three-dim...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2009
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| _version_ | 1797089178105675776 |
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| author | Paesen, G Siebold, C Dallas, M Peers, C Harlos, K Nuttall, P Nunn, M Stuart, D Esnouf, R |
| author_facet | Paesen, G Siebold, C Dallas, M Peers, C Harlos, K Nuttall, P Nunn, M Stuart, D Esnouf, R |
| author_sort | Paesen, G |
| collection | OXFORD |
| description | Ra-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI proteins. We report the detection, purification and characterization of the function of Ra-KLP. In addition, determination of the three-dimensional crystal structure of Ra-KLP at 1.6 A resolution using sulphur single-wavelength anomalous dispersion reveals that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by beta-strands. Even more unusually, the N-terminal portion of the polypeptide chain is pinned to the "Kunitz head" by two disulphide bridges not found in classical Kunitz/BPTI proteins. The disulphide bond pattern has been further altered by the loss of the bridge that normally stabilizes the protease-binding loop. Consistent with the conversion of this loop into a beta-strand, Ra-KLP shows no significant anti-protease activity; however, it activates maxiK channels in an in vitro system, suggesting a potential mechanism for regulating host blood supply during feeding. |
| first_indexed | 2024-03-07T03:00:41Z |
| format | Journal article |
| id | oxford-uuid:b0de5c18-3a86-4d20-88a0-23c7f84b88a8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:00:41Z |
| publishDate | 2009 |
| record_format | dspace |
| spelling | oxford-uuid:b0de5c18-3a86-4d20-88a0-23c7f84b88a82022-03-27T03:59:33ZAn ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b0de5c18-3a86-4d20-88a0-23c7f84b88a8EnglishSymplectic Elements at Oxford2009Paesen, GSiebold, CDallas, MPeers, CHarlos, KNuttall, PNunn, MStuart, DEsnouf, RRa-KLP, a 75 amino acid protein secreted by the salivary gland of the brown ear tick Rhipicephalus appendiculatus has a sequence resembling those of Kunitz/BPTI proteins. We report the detection, purification and characterization of the function of Ra-KLP. In addition, determination of the three-dimensional crystal structure of Ra-KLP at 1.6 A resolution using sulphur single-wavelength anomalous dispersion reveals that much of the loop structure of classical Kunitz domains, including the protruding protease-binding loop, has been replaced by beta-strands. Even more unusually, the N-terminal portion of the polypeptide chain is pinned to the "Kunitz head" by two disulphide bridges not found in classical Kunitz/BPTI proteins. The disulphide bond pattern has been further altered by the loss of the bridge that normally stabilizes the protease-binding loop. Consistent with the conversion of this loop into a beta-strand, Ra-KLP shows no significant anti-protease activity; however, it activates maxiK channels in an in vitro system, suggesting a potential mechanism for regulating host blood supply during feeding. |
| spellingShingle | Paesen, G Siebold, C Dallas, M Peers, C Harlos, K Nuttall, P Nunn, M Stuart, D Esnouf, R An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title | An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title_full | An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title_fullStr | An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title_full_unstemmed | An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title_short | An ion-channel modulator from the saliva of the brown ear tick has a highly modified Kunitz/BPTI structure. |
| title_sort | ion channel modulator from the saliva of the brown ear tick has a highly modified kunitz bpti structure |
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