Staphylococcus aureus SdrE captures complement factor H's C-terminus via a novel 'close, dock, lock and latch'...

Area of Science:

• Immunology
• Structural Biology
• Microbiology

Background:

• Complement factor H (CFH) regulates the alternative complement pathway, protecting host cells from immune attack.
• Staphylococcus aureus uses surface protein SdrE to bind CFH, a strategy for immune evasion.
• The molecular basis of SdrE-mediated CFH binding and immune evasion is not well understood.

Purpose of the Study:

• To elucidate the molecular mechanism by which Staphylococcus aureus SdrE binds complement factor H (CFH).
• To characterize the structural basis of the interaction between SdrE and CFH.
• To identify the specific regions involved in this immune evasion strategy.

Main Methods:

• Crystallography was used to determine the structures of SdrE N2N3 domains (SdrE_N2N3) and the SdrE_N2N3-CFH^1206-1226 complex.
• Structural comparison of the CFH-SdrE complex with other CFH structures.
• Analysis of conformational changes in SdrE upon CFH binding.

Main Results:

• A novel binding site at the C-terminus of CFH (CFH^1206-1226) was identified, interacting with SdrE_N2N3.
• The crystal structure revealed CFH's C-terminal tail inserting into SdrE's ligand-binding groove.
• SdrE_N2N3 undergoes a significant conformational change, adopting a 'close, dock, lock and latch' (CDLL) mechanism upon CFH binding.

Conclusions:

• SdrE acts as a molecular 'clamp' to capture CFH's C-terminal tail via the CDLL mechanism.
• This interaction sequesters CFH on the surface of *S. aureus*, facilitating immune evasion.
• The findings provide critical insights into bacterial immune evasion strategies targeting the complement system.