8EC3

The crystal structure of the complement inhibitory domain of Borrelia hermsii FbpC.

Summary for 8EC3

• Entry DOI: 10.2210/pdb8ec3/pdb
• Descriptor: Fibronectin-binding protein, MAGNESIUM ION (3 entities in total)
• Functional Keywords: borrelia hermsii, complement, inhibitor, immune system
• Biological source: Borrelia hermsii HS1
• Total number of polymer chains: 1
• Total formula weight: 18905.56

Authors

Booth, C.E.,Garcia, B.L. (deposition date: 2022-09-01, release date: 2023-06-07, Last modification date: 2024-04-03)

Primary citation

Roy, S.,Booth Jr., C.E.,Powell-Pierce, A.D.,Schulz, A.M.,Skare, J.T.,Garcia, B.L.
Conformational dynamics of complement protease C1r inhibitor proteins from Lyme disease- and relapsing fever-causing spirochetes.
J.Biol.Chem., 299:104972-104972, 2023

PubMed Abstract: Borrelial pathogens are vector-borne etiological agents known to cause Lyme disease, relapsing fever, and Borrelia miyamotoi disease. These spirochetes each encode several surface-localized lipoproteins that bind components of the human complement system to evade host immunity. One borrelial lipoprotein, BBK32, protects the Lyme disease spirochete from complement-mediated attack via an alpha helical C-terminal domain that interacts directly with the initiating protease of the classical complement pathway, C1r. In addition, the B. miyamotoi BBK32 orthologs FbpA and FbpB also inhibit C1r, albeit via distinct recognition mechanisms. The C1r-inhibitory activities of a third ortholog termed FbpC, which is found exclusively in relapsing fever-causing spirochetes, remains unknown. Here, we report the crystal structure of the C-terminal domain of Borrelia hermsii FbpC to a limiting resolution of 1.5 Å. We used surface plasmon resonance and assays of complement function to demonstrate that FbpC retains potent BBK32-like anticomplement activities. Based on the structure of FbpC, we hypothesized that conformational dynamics of the complement inhibitory domains of borrelial C1r inhibitors may differ. To test this, we utilized the crystal structures of the C-terminal domains of BBK32, FbpA, FbpB, and FbpC to carry out molecular dynamics simulations, which revealed borrelial C1r inhibitors adopt energetically favored open and closed states defined by two functionally critical regions. Taken together, these results advance our understanding of how protein dynamics contribute to the function of bacterial immune evasion proteins and reveal a surprising plasticity in the structures of borrelial C1r inhibitors.

PubMed: 37380082
DOI: 10.1016/j.jbc.2023.104972

Experimental method

X-RAY DIFFRACTION (1.5 Å)