6V8Q

Structure of an inner membrane protein required for PhoPQ regulated increases in outer membrane cardiolipin

Summary for 6V8Q

• Entry DOI: 10.2210/pdb6v8q/pdb
• Descriptor: Inner membrane protein YejM, CALCIUM ION, PHOSPHATE ION, ... (5 entities in total)
• Functional Keywords: pbga, cl transport, phopq, outer membrane barrier, membrane protein
• Biological source: Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S
• Total number of polymer chains: 2
• Total formula weight: 143190.07

Authors

Fan, J.,Miller, S. (deposition date: 2019-12-11, release date: 2020-03-18, Last modification date: 2024-04-03)

Primary citation

Fan, J.,Petersen, E.M.,Hinds, T.R.,Zheng, N.,Miller, S.I.
Structure of an Inner Membrane Protein Required for PhoPQ-Regulated Increases in Outer Membrane Cardiolipin.
Mbio, 11:-, 2020

PubMed Abstract: The subsp. serovar Typhimurium PhoPQ two-component system is activated within the intracellular phagosome environment, where it promotes remodeling of the outer membrane and resistance to innate immune antimicrobial peptides. Maintenance of the PhoPQ-regulated outer membrane barrier requires PbgA, an inner membrane protein with a transmembrane domain essential for growth, and a periplasmic domain required for PhoPQ-activated increases in outer membrane cardiolipin. Here, we report the crystal structure of cardiolipin-bound PbgA, adopting a novel transmembrane fold that features a cardiolipin binding site in close proximity to a long and deep cleft spanning the lipid bilayer. The end of the cleft extends into the periplasmic domain of the protein, which is structurally coupled to the transmembrane domain via a functionally critical C-terminal helix. In conjunction with a conserved putative catalytic dyad situated at the middle of the cleft, our structural and mutational analyses suggest that PbgA is a multifunction membrane protein that mediates cardiolipin transport, a function essential for growth, and perhaps catalysis of an unknown enzymatic reaction. Gram-negative bacteria cause many types of infections and have become increasingly resistant to available antibiotic drugs. The outer membrane serves as an important barrier that protects bacteria against antibiotics and other toxic compounds. This outer membrane barrier function is regulated when bacteria are in host environments, and the protein PbgA contributes significantly to this increased barrier function by transporting cardiolipin to the outer membrane. We determined the crystal structure of PbgA in complex with cardiolipin and propose a model for its function. Knowledge of the mechanisms of outer membrane assembly and integrity can greatly contribute to the development of new and effective antibiotics, and this structural information may be useful in this regard.

PubMed: 32047135
DOI: 10.1128/mBio.03277-19

Experimental method

X-RAY DIFFRACTION (2.69958498172 Å)