Renwick Dobson, James S. Davies, Michael J. Currie and Rachel A. North with Daniela M. Remus, Michael C. Newton-Vesty, Gayan S. Abeysekera (University of Canterbury) with Peter D. Mace and Sam A. Jamieson (University of Otago), Jack M. Copping and Jane R. Allison (University of Auckland and international collaborators (University of Calabria, Stockholm University, Purdue University, University of Gothenburg, Stanford University School of Medicine)
Tripartite ATP-independent periplasmic (TRAP) transporters play key roles in bacterial colonisation, pathogenesis and antimicrobial resistance. These transporters help bacteria absorb nutrients.
Unlike many transporters, TRAP systems rely on a three-part structure and do not use ATP (energy molecules) to function. Despite their critical roles in disease and potential as antimicrobial targets, the coupling mechanism between the transporter and the substrate-binding protein are poorly understood.
Using a combination Small Angle X-ray Scattering (SAXS) and Macromolecular Crystallography (MC) beamlines, the research team captured detailed 3D images of a TRAP transporter called SiaQM from the bacterium Photobacterium profundum. They found that SiaQM works like an “elevator”, moving nutrients across the membrane using sodium ions, but only when a helper protein (SiaP) delivers the nutrient.
The researchers proposed a new model for how TRAP transporters work, calling it an “elevator-with-an-operator” mechanism—where the helper protein acts like an operator guiding the elevator.
Understanding how TRAP transporters work could help scientists develop new antibiotics that block nutrient uptake in harmful bacteria. The research advances our general understanding of membrane transport mechanisms, which are essential in biology and medicine.
The structural insights will help design targeted drugs that interfere with bacterial transport systems without affecting human cells (humans do not have TRAP transporters).
Reference:
Davies JS, Currie MJ, North RA, Scalise M, Wright JD, Copping JM, Remus DM, Gulati A, Morado DR, Jamieson SA, Newton-Vesty MC, Abeysekera GS, Ramaswamy S, Friemann R, Wakatsuki S, Allison JR, Indiveri C, Drew D, Mace PD and Dobson RCJ. 2023. Structure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter. Nature Communications 14: 1120. https://doi.org/10.1038/s41467-023-36590-1
