Structural and SAXS analysis of Tle5-Tli5 complex reveals a novel inhibition mechanism of H2-T6SS in Pseudomonas aeruginosa

Protein Sci. 2017 Oct;26(10):2083-2091. doi: 10.1002/pro.3246. Epub 2017 Aug 30.

Abstract

Widely spread in Gram-negative bacteria, the type VI secretion system (T6SS) secretes many effector-immunity protein pairs to help the bacteria compete against other prokaryotic rivals, and infect their eukaryotic hosts. Tle5 and Tle5B are two phospholipase effector protein secreted by T6SS of Pseudomonas aeruginosa. They can facilitate the bacterial internalization process into human epithelial cells by interacting with Akt protein of the PI3K-Akt signal pathway. Tli5 and PA5086-5088 are cognate immunity proteins of Tle5 and Tle5B, respectively. They can interact with their cognate effector proteins to suppress their virulence. Here, we report the crystal structure of Tli5 at 2.8Å resolution and successfully fit it into the Small angle X-ray scattering (SAXS) model of the complete Tle5-Tli5 complex. We identified two important motifs in Tli5 through sequence and structural analysis. One is a conserved loop-β-hairpin motif that exists in the Tle5 immunity homologs, the other is a long and sharp α-α motif that directly interacts with Tle5 according to SAXS data. We also distinguished the structural features of Tle5 and Tle5B family immunity proteins. Together, our work provided insights into a novel inhibition mechanism that may enhance our understanding of phospholipase D family proteins.

Keywords: SAXS; X-ray crystallography; immunity protein; type VI secretion system.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Escherichia coli / genetics
  • Models, Molecular
  • Phospholipases / metabolism
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Scattering, Small Angle
  • Static Electricity
  • Type VI Secretion Systems / chemistry*
  • Type VI Secretion Systems / genetics
  • Type VI Secretion Systems / metabolism*
  • X-Ray Diffraction

Substances

  • Bacterial Proteins
  • Recombinant Proteins
  • Type VI Secretion Systems
  • Phospholipases