Structural Dynamics of ABC Transporter MsbA during Functional Activity

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06581
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43040:Biophysics-related
• Research Institution: Kanazawa University
• Principal Investigator: NGO XUANKIEN 金沢大学, ナノ生命科学研究所, 特任助教 (60778190)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ABC transporter / Lipid A / High-speed AFM

Outline of Final Research Achievements

Our recent precise analyses on structural dynamics of bacterial ABC transporter MsbA using High-speed Atomic Force Microscopy (HS-AFM) show that lipid A/lipopolysaccharide (LPS) after flipping across inner membrane (IM) remains in the transmembrane domains (TMDs) core of MsbA even during many ATPase cycles. Bound ATP locks two NBDs in closed conformation for maintaining an outward-facing conformation that facilitates the flipping of lipid A/LPS across IM. ATPase activity of MsbA (ATP→ADP.Pi) may always go on during and after flipping of lipid A/LPS across membrane. When lipid A/LPS is trapped inside TMDs core of MsbA bound ATP, we do not observe the conformational transitions between inward-facing and outward-facing as reported in the previous hypotheses. Currently, we continue this study to unravel the correlation between the structural dynamics and transport activity of MsbA.

Free Research Field

Biophysics

Academic Significance and Societal Importance of the Research Achievements

Our study is important to precisely understand the working mechanism of lipid A transport from the IM to OM by MsbA in bacteria.