title: The transmembrane protein KpOmpA anchoring the outer membrane of Klebsiella pneumoniae unfolds and refolds in response to tensile load.
abstract: In Klebsiella pneumoniae the transmembrane β-barrel forming outer membrane protein KpOmpA mediates adhesion to a wide range of immune effector cells, thereby promoting respiratory tract and urinary infections. As major transmembrane protein OmpA stabilizes Gram-negative bacteria by anchoring their outer membrane to the peptidoglycan layer. Adhesion, osmotic pressure, hydrodynamic flow, and structural deformation apply mechanical stress to the bacterium. This stress can generate tensile load to the peptidoglycan-binding domain (PGBD) of KpOmpA. To investigate how KpOmpA reacts to mechanical stress, we applied a tensile load to the PGBD and observed a detailed unfolding pathway of the transmembrane β-barrel. Each step of the unfolding pathway extended the polypeptide connecting the bacterial outer membrane to the peptidoglycan layer and absorbed mechanical energy. After relieving the tensile load, KpOmpA reversibly refolded back into the membrane. These results suggest that bacteria may reversibly unfold transmembrane proteins in response to mechanical stress.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Bosshart
authors.forename: Iordan
authors.initials: I
authors.lastname: Iordanov
authors.forename: Carlos
authors.initials: C
authors.lastname: Garzon-Coral
authors.forename: Pascal
authors.initials: P
authors.lastname: Demange
authors.forename: Andreas
authors.initials: A
authors.lastname: Engel
authors.forename: Alain
authors.initials: A
authors.lastname: Milon
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry*; D002448:Cell Adhesion; D057446:Hydrodynamics; D008958:Models, Molecular; D009997:Osmotic Pressure; D010457:Peptidoglycan / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D013314:Stress, Mechanical
chemical_list: D001425:Bacterial Outer Membrane Proteins; D010457:Peptidoglycan; C078167:OMPA outer membrane proteins