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Phosphatidylglyerol Lipid Binding at the Active Site of an Intramembrane Protease.

ABSTRACT: Transmembrane substrate cleavage by the small Escherichia coli rhomboid protease GlpG informs on mechanisms by which lipid interactions shape reaction coordinates of membrane-embedded enzymes. Here, I review and discuss new work on the molecular picture of protein-lipid interactions that might govern the formation of the substrate-enzyme complex in fluid lipid membranes. Negatively charged PG-type lipids are of particular interest, because they are a major component of bacterial membranes. Atomistic computer simulations indicate POPG and DOPG lipids bridge remote parts of GlpG and might pre-occupy the substrate-docking site. Inhibition of catalytic activity by PG lipids could arise from ligand-like lipid binding at the active site, which could delay or prevent substrate docking. Dynamic protein-lipid H-bond networks, water access to the active site, and fluctuations in the orientation of GlpG suggest that GlpG has lipid-coupled dynamics that could shape the energy landscape of transmembrane substrate docking.

SUBMITTER: Bondar AN

PROVIDER: S-EPMC7688093 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Phosphatidylglyerol Lipid Binding at the Active Site of an Intramembrane Protease.

Bondar Ana-Nicoleta AN

The Journal of membrane biology 20201118 6

Transmembrane substrate cleavage by the small Escherichia coli rhomboid protease GlpG informs on mechanisms by which lipid interactions shape reaction coordinates of membrane-embedded enzymes. Here, I review and discuss new work on the molecular picture of protein-lipid interactions that might govern the formation of the substrate-enzyme complex in fluid lipid membranes. Negatively charged PG-type lipids are of particular interest, because they are a major component of bacterial membranes. Atomi ...[more]

PMID: 33210155

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