6RPT
Structure of tick complement inhibitor CirpT1 complexed with macroglobubulin domain 4 of human complement C5
Summary for 6RPT
| Entry DOI | 10.2210/pdb6rpt/pdb |
| Related | 5HCC |
| Descriptor | Complement C5, Putative 8.9 kDa family member, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | complement, inhibitor, innate immunity, inflammation, c5, terminal pathway inhibitor, immunosuppressant |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 80849.24 |
| Authors | Reichhardt, M.P.,Lea, S.M.,Johnson, S. (deposition date: 2019-05-14, release date: 2020-01-08, Last modification date: 2024-11-13) |
| Primary citation | Reichhardt, M.P.,Johnson, S.,Tang, T.,Morgan, T.,Tebeka, N.,Popitsch, N.,Deme, J.C.,Jore, M.M.,Lea, S.M. An inhibitor of complement C5 provides structural insights into activation. Proc.Natl.Acad.Sci.USA, 117:362-370, 2020 Cited by PubMed Abstract: The complement system is a crucial part of innate immune defenses against invading pathogens. The blood-meal of the tick 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. PubMed: 31871188DOI: 10.1073/pnas.1909973116 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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