Structural Insights into the Yersinia pestis Outer Membrane Protein Ail in Lipid Bilayers.
Samit Kumar DuttaYong YaoFrancesca M MarassiPublished in: The journal of physical chemistry. B (2017)
Yersinia pestis the causative agent of plague, is highly pathogenic and poses very high risk to public health. The outer membrane protein Ail (Adhesion invasion locus) is one of the most highly expressed proteins on the cell surface of Y. pestis, and a major target for the development of medical countermeasures. Ail is essential for microbial virulence and is critical for promoting the survival of Y. pestis in serum. Structures of Ail have been determined by X-ray diffraction and solution NMR spectroscopy, but the protein's activity is influenced by the detergents in these samples, underscoring the importance of the surrounding environment for structure-activity studies. Here we describe the backbone structure of Ail, determined in lipid bilayer nanodiscs, using solution NMR spectroscopy. We also present solid-state NMR data obtained for Ail in membranes containing lipopolysaccharide (LPS), a major component of the bacterial outer membranes. The protein in lipid bilayers, adopts the same eight-stranded β-barrel fold observed in the crystalline and micellar states. The membrane composition, however, appears to have a marked effect on protein dynamics, with LPS enhancing conformational order and slowing down the 15N transverse relaxation rate. The results provide information about the way in which an outer membrane protein inserts and functions in the bacterial membrane.
Keyphrases
- solid state
- public health
- molecular dynamics simulations
- inflammatory response
- high resolution
- binding protein
- protein protein
- cell surface
- fatty acid
- staphylococcus aureus
- amino acid
- healthcare
- magnetic resonance
- pseudomonas aeruginosa
- single molecule
- microbial community
- magnetic resonance imaging
- toll like receptor
- small molecule
- cell migration
- biofilm formation
- molecular dynamics
- big data
- deep learning
- room temperature
- immune response
- artificial intelligence
- crystal structure
- global health