7S0R

Crystal Structure of a Complement Factor H-binding Fragment within the B75KN Region of the Group B Streptococcus Beta Antigen C Protein

7S0R の概要

• エントリーDOI: 10.2210/pdb7s0r/pdb
• 分子名称: C protein beta antigen (1 entity in total)
• 機能のキーワード: cell-surface protein, immune evasion, complement, factor h, protein binding
• 由来する生物種: Streptococcus agalactiae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 24194.30

構造登録者

Xu, X.,Geisbrecht, B.V. (登録日: 2021-08-31, 公開日: 2021-12-15, 最終更新日: 2024-11-13)

主引用文献

Xu, X.,Lewis Marffy, A.L.,Keightley, A.,McCarthy, A.J.,Geisbrecht, B.V.
Group B Streptococcus Surface Protein beta : Structural Characterization of a Complement Factor H-Binding Motif and Its Contribution to Immune Evasion.
J Immunol., 208:1232-1247, 2022

PubMed Abstract: The β protein from group B (GBS) is a ∼132-kDa, cell-surface exposed molecule that binds to multiple host-derived ligands, including complement factor H (FH). Many details regarding this interaction and its significance to immune evasion by GBS remain unclear. In this study, we identified a three-helix bundle domain within the C-terminal half of the B75KN region of β as the major FH-binding determinant and determined its crystal structure at 2.5 Å resolution. Analysis of this structure suggested a role in FH binding for a loop region connecting helices α1 and α2, which we confirmed by mutagenesis and direct binding studies. Using a combination of protein cross-linking and mass spectrometry, we observed that B75KN bound to complement control protein (CCP)3 and CCP4 domains of FH. Although this binding site lies within a complement regulatory region of FH, we determined that FH bound by β retained its decay acceleration and cofactor activities. Heterologous expression of β by resulted in recruitment of FH to the bacterial surface and a significant reduction of C3b deposition following exposure to human serum. Surprisingly, we found that FH binding by β was not required for bacterial resistance to phagocytosis by neutrophils or killing of bacteria by whole human blood. However, loss of the B75KN region significantly diminished bacterial survival in both assays. Although our results show that FH recruited to the bacterial surface through a high-affinity interaction maintains key complement-regulatory functions, they raise questions about the importance of FH binding to immune evasion by GBS as a whole.

PubMed: 35110419
DOI: 10.4049/jimmunol.2101078

実験手法

X-RAY DIFFRACTION (2.5 Å)