An inhibitor of complement C5 provides structural insights into activation
The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick Rhipicephalus pulchellus lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva...
| मुख्य लेखकों: | , , , , , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
National Academy of Sciences
2019
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| _version_ | 1826292326708805632 |
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| author | Reichhardt, M Johnson, S Tang, T Morgan, T Tebeka, N Popitsch, N Deme, J Jore, M Lea, S |
| author_facet | Reichhardt, M Johnson, S Tang, T Morgan, T Tebeka, N Popitsch, N Deme, J Jore, M Lea, S |
| author_sort | Reichhardt, M |
| collection | OXFORD |
| description | The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick Rhipicephalus pulchellus lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway. |
| first_indexed | 2024-03-07T03:12:58Z |
| format | Journal article |
| id | oxford-uuid:b4d34415-f847-462e-8c8f-2bb5a62b4b6a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:12:58Z |
| publishDate | 2019 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:b4d34415-f847-462e-8c8f-2bb5a62b4b6a2022-03-27T04:29:01ZAn inhibitor of complement C5 provides structural insights into activationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b4d34415-f847-462e-8c8f-2bb5a62b4b6aEnglishSymplectic Elements at OxfordNational Academy of Sciences2019Reichhardt, MJohnson, STang, TMorgan, TTebeka, NPopitsch, NDeme, JJore, MLea, SThe complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick Rhipicephalus pulchellus lasts for days, and the tick must therefore rely on inhibitors to counter complement activation. We have identified a class of inhibitors from tick saliva, the CirpT family, and generated detailed structural data revealing their mechanism of action. We show direct binding of a CirpT to complement C5 and have determined the structure of the C5-CirpT complex by cryoelectron microscopy. This reveals an interaction with the peripheral macro globulin domain 4 (C5_MG4) of C5. To achieve higher resolution detail, the structure of the C5_MG4-CirpT complex was solved by X-ray crystallography (at 2.7 Å). We thus present the fold of the CirpT protein family, and provide detailed mechanistic insights into its inhibitory function. Analysis of the binding interface reveals a mechanism of C5 inhibition, and provides information to expand our biological understanding of the activation of C5, and thus the terminal complement pathway. |
| spellingShingle | Reichhardt, M Johnson, S Tang, T Morgan, T Tebeka, N Popitsch, N Deme, J Jore, M Lea, S An inhibitor of complement C5 provides structural insights into activation |
| title | An inhibitor of complement C5 provides structural insights into activation |
| title_full | An inhibitor of complement C5 provides structural insights into activation |
| title_fullStr | An inhibitor of complement C5 provides structural insights into activation |
| title_full_unstemmed | An inhibitor of complement C5 provides structural insights into activation |
| title_short | An inhibitor of complement C5 provides structural insights into activation |
| title_sort | inhibitor of complement c5 provides structural insights into activation |
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