Ikoma, Japan—Gram-negative bacteria are responsible for causing several infections that are hard to treat, owing to their high resistance to antibiotics. These bacteria possess an exterior most layer called the outer membrane that acts like a protective barrier. Serving as the cell's interface with the outside world, the outer membrane contains specialized proteins that perform multiple functions such as nutrient transport and environment sensing. The localization of these outer membrane proteins is achieved through the combined action of several key players, including the SurA chaperone and the β-barrel assembly machinery (BAM) complex.
SurA acts as a periplasmic chaperone that binds unfolded outer membrane proteins (OMPs) and delivers them to BAM, where they are correctly folded and inserted into the outer membrane. Although many aspects of BAM-mediated OMP assembly are well understood, how SurA physically transfers its OMP cargo to BAM remains unclear.
In a recent study, a research team led by Assistant Professor Ryoji Miyazaki from Nara Institute of Science and Technology (NAIST), Japan, set out to fill this knowledge gap. Their work, which will be published in Nature Communications on September 4, 2026, reveals that SurA adopts multiple conformations while associated with BAM and identifies interactions that may help move its OMP cargo toward the assembly machinery. The paper was co-authored by Assistant Professor Hidetaka Kohga, Ms. Nami Matsuoka, Mr. Wataru Yoshimoto, Mr. Yutaro S. Takahashi, and Professor Tomoya Tsukazaki from NAIST; Mr. Yuki Maruno and Associate Professor Takuya Shiota from the University of Miyazaki, Japan; Dr. Dede Heri Yuli Yanto and Dr. Yudhi Nugraha from the National Research and Innovation Agency, Indonesia; and Dr. Hideki Shigematsu from the Japan Synchrotron Radiation Research Institute, Japan.
The researchers used cryo-electron microscopy (cryo-EM) to visualize the SurA–BAM complex. Cryo-EM analysis revealed two distinct structures in which either the SurA Core domain alone or the Core and P1 domains were resolved. Because the flexible P2 domain remained unresolved, the researchers introduced specific mutations in SurA to create disulfide bonds at carefully calculated positions between SurA and BAM, stabilizing particular conformations for structural analysis.
This approach enabled the team to capture four distinct structural snapshots of SurA bound to BAM (Core-only, P1-visible, P2-visible, and P1/P2-visible), illustrating how SurA reconfigures itself to assist with OMP delivery. "Our structural and biochemical analyses have revealed key aspects of the SurA–BAM-mediated delivery mechanism. The four cryo-EM structures identified suggest that SurA undergoes large conformational changes to transfer OMP substrates to BAM," explains Dr. Miyazaki. Structural comparison showed that SurA's cargo-carrying Core domain moves progressively closer to BAM, while its two flexible domains, P1 and P2, adopt different conformations. The P1 domain appears to regulate the function of the Core domain, while the P2 domain interacts with a BAM component called BamE, helping to position SurA closer to the assembly machinery. Disrupting this interaction reduced OMP assembly, highlighting its importance.
Because this delivery system is important for building the outer membrane, it could also present potential targets for antibacterial agents. "The outer membrane is a major protective barrier of Gram-negative bacteria and contributes to their resistance to many antibiotics. Understanding how OMPs are assembled may therefore help us identify new ways to weaken this barrier and combat pathogenic or antibiotic-resistant bacteria," concludes Dr. Miyazaki.
