Conserved Omp85 lid-lock structure and substrate recognition in FhaC

Timm Maier (1) , Bernard Clantin (2) , Fabian Gruss (1) , Frederique Dewitte (2) , Anne-Sophie Delattre (3) , Françoise Jacob-Dubuisson (3) , Sebastian Hiller (1) , Vincent Villeret (2)

1 Unibas - Université de Bâle = University of Basel = Basel Universität
2 UGSF - Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576
3 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204

Omp85 proteins mediate translocation of polypeptide substrates across and into cellular membranes. They share a common architecture comprising substrate-interacting POTRA domains, a C-terminal 16-stranded β-barrel pore and two signature motifs located on the inner barrel wall and at the tip of the extended L6 loop. The observation of two distinct conformations of the L6 loop in the available Omp85 structures previously suggested a functional role of conformational changes in L6 in the Omp85 mechanism. Here we present a 2.5 Å resolution structure of a variant of the Omp85 secretion protein FhaC, in which the two signature motifs interact tightly and form the conserved 'lid lock'. Reanalysis of previous structural data shows that L6 adopts the same, conserved resting state position in all available Omp85 structures. The FhaC variant structure further reveals a competitive mechanism for the regulation of substrate binding mediated by the linker to the N-terminal plug helix H1.

Mots clés: Sequence Homology; Amino Acid; Amino Acid Sequence; Bacterial Outer Membrane Proteins; Escherichia coli Proteins; X-Ray Diffraction; Substrate Specificity; Molecular Sequence Data; Protein Conformation

Domaines: Biologie structurale [q-bio.BM]; Bactériologie

Timm Maier, Bernard Clantin, Fabian Gruss, Frederique Dewitte, Anne-Sophie Delattre, et al.. Conserved Omp85 lid-lock structure and substrate recognition in FhaC. Nature Communications, 2015, 6, pp.7452. ⟨10.1038/ncomms8452⟩. ⟨hal-03182009⟩