Structure and specificity of the Type VI secretion system ClpV-TssC interaction in enteroaggregative Escherichia coli

Badreddine Douzi (1) , Yannick R Brunet (2) , Silvia Spinelli (1) , Valentine Lensi (2) , Stephanie Blangy (3) , Anant Kumar (2) , Laure Journet (2) , Pierre Legrand (4) , E. Cascales (2) , Christian Cambillau (1)

1 AFMB - Architecture et fonction des macromolécules biologiques
2 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires
3 BVME - Biologie végétale et microbiologie environnementale - UMR7265
4 SSOLEIL - Synchrotron SOLEIL

The Type VI secretion system (T6SS) is a versatile machine that delivers toxins into either eukaryotic or bacterial cells. It thus represents a key player in bacterial pathogenesis and inter-bacterial competition. Schematically, the T6SS can be viewed as a contractile tail structure anchored to the cell envelope. The contraction of the tail sheath propels the inner tube loaded with effectors towards the target cell. The components of the contracted tail sheath are then recycled by the ClpV AAA+ ATPase for a new cycle of tail elongation. The T6SS is widespread in Gram-negative bacteria and most of their genomes carry several copies of T6SS gene clusters, which might be activated in different conditions. Here, we show that the ClpV ATPases encoded within the two T6SS gene clusters of enteroaggregative Escherichia coli are not interchangeable and specifically participate to the activity of their cognate T6SS. Here we show that this specificity is dictated by interaction between the ClpV N-terminal domains and the N-terminal helices of their cognate TssC1 proteins. We also present the crystal structure of the ClpV1 N-terminal domain, alone or in complex with the TssC1 N-terminal peptide, highlighting the commonalities and diversities in the recruitment of ClpV to contracted sheaths.

Keywords: Adenosine Triphosphatases/*chemistry/genetics; Crystallography, X-Ray; Escherichia coli/*enzymology/genetics; Escherichia coli Proteins/*chemistry/genetics; *Multigene Family; Type VI Secretion Systems/*chemistry/genetics

Keywords: Protein Domains

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Molecular Networks [q-bio.MN]; Life Sciences [q-bio]; Microbiology and Parasitology; Bacteriology

Badreddine Douzi, Yannick R Brunet, Silvia Spinelli, Valentine Lensi, Stephanie Blangy, et al.. Structure and specificity of the Type VI secretion system ClpV-TssC interaction in enteroaggregative Escherichia coli. Scientific Reports, 2016, 6 (1), ⟨10.1038/srep34405⟩. ⟨hal-01780690⟩