7mzt | pdb_00007mzt

Borrelia burgdorferi BBK32-C in complex with an autolytic fragment of human C1r at 4.1A

spinqualitylabelsall models 7mzt, resolution 4.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7mzt is a 3 chain structure with sequence from Borreliella burgdorferi B31 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.07Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C1R_HUMAN C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system. Publication Abstract from PubMed Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, 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. A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes.,Garrigues RJ, Powell-Pierce AD, Hammel M, Skare JT, Garcia BL J Immunol. 2021 Dec 1;207(11):2856-2867. doi: 10.4049/jimmunol.2100815. Epub 2021 , Nov 10. PMID:34759015 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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