7MZT
Borrelia burgdorferi BBK32-C in complex with an autolytic fragment of human C1r at 4.1A
Summary for 7MZT
| Entry DOI | 10.2210/pdb7mzt/pdb |
| Descriptor | Complement C1r subcomponent heavy chain, Complement C1r subcomponent light chain, Fibronectin-binding protein BBK32, ... (4 entities in total) |
| Functional Keywords | lyme disease spirochete, borrelia burgdorferi, complement system, classical pathway, protease inhibitor, protein binding |
| Biological source | Borrelia burgdorferi (strain ATCC 35210 / B31 / CIP 102532 / DSM 4680) More |
| Total number of polymer chains | 3 |
| Total formula weight | 63479.99 |
| Authors | Garcia, B.L. (deposition date: 2021-05-24, release date: 2021-09-29, Last modification date: 2024-11-20) |
| Primary citation | Garrigues, R.J.,Powell-Pierce, A.D.,Hammel, M.,Skare, J.T.,Garcia, B.L. A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes. J Immunol., 207:2856-2867, 2021 Cited by PubMed Abstract: Complement evasion is a hallmark of extracellular microbial pathogens such as , the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography-coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1') and reveals a surprising role for C1r B loop-interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway-specific inhibition by a human pathogen. PubMed: 34759015DOI: 10.4049/jimmunol.2100815 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (4.07 Å) |
Structure validation
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