Architecture and conformational dynamics of the BAM-SurA holo insertase complex

Area of Science:

• Structural Biology
• Microbiology
• Biochemistry

Background:

• Gram-negative bacteria require the β-barrel assembly machinery (BAM) complex for proper folding of outer membrane proteins.
• The role of the periplasmic chaperone, survival protein A (SurA), in delivering substrates to BAM is not fully understood.

Purpose of the Study:

• To elucidate the mechanism by which SurA facilitates substrate delivery to the BAM complex.
• To determine the structure of the holo insertase complex, comprising SurA bound to BAM.

Main Methods:

• High-resolution cryo-electron microscopy (cryo-EM) was employed to capture four distinct states of the SurA-BAM complex.
• Three-dimensional variability analysis was utilized to assess the dynamic range of the complex.

Main Results:

• The holo insertase complex exhibits significant conformational flexibility, with SurA undergoing a large swinging motion between two states.
• This SurA motion is independent of the conformational changes (opening and closing) of the BamA barrel.
• Conformational coupling was observed between the SurA swing state and the BamC carboxyl-terminal helix grip domain.

Conclusions:

• SurA delivers outer membrane protein substrates to BAM through a concerted, dynamic mechanism.
• This process involves a gated pathway through accessory BAM proteins to the membrane insertion site.