6za2 | pdb_00006za2

Crystal structure of dimeric latent PorU from Porphyromonas gingivalis

spinqualitylabelsall models 6za2, resolution 3.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6za2 is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Porphyromonas gingivalis is a keystone pathogen of the human dysbiotic oral microbiome that causes severe periodontitis. It employs a type-IX secretion system (T9SS) to shuttle proteins across the outer membrane (OM) for virulence. Uniquely, T9SS cargoes carry a C-terminal domain (CTD) as a secretion signal, which is cleaved and replaced with anionic lipopolysaccharide by transpeptidation for extracellular anchorage to the OM. Both reactions are carried out by PorU, the only known dual-function, C-terminal signal peptidase and sortase. PorU is itself secreted by the T9SS, but its CTD is not removed; instead, intact PorU combines with PorQ, PorV, and PorZ in the OM-inserted "attachment complex." Herein, we revealed that PorU transits between active monomers and latent dimers and solved the crystal structure of the approximately 260-kDa dimer. PorU has an elongated shape approximately 130 A in length and consists of seven domains. The first three form an intertwined N-terminal cluster likely engaged in substrate binding. They are followed by a gingipain-type catalytic domain (CD), two immunoglobulin-like domains (IGL), and the CTD. In the first IGL, a long "latency beta-hairpin" protrudes approximately 30 A from the surface to form an intermolecular beta-barrel with beta-strands from the symmetric CD, which is in a latent conformation. Homology modeling of the competent CD followed by in vivo validation through a cohort of mutant strains revealed that PorU is transported and functions as a monomer through a C(690)/H(657) catalytic dyad. Thus, dimerization is an intermolecular mechanism for PorU regulation to prevent untimely activity until joining the attachment complex. Intermolecular latency regulates the essential C-terminal signal peptidase and sortase of the Porphyromonas gingivalis type-IX secretion system.,Mizgalska D, Goulas T, Rodriguez-Banqueri A, Veillard F, Madej M, Malecka E, Szczesniak K, Ksiazek M, Widziolek M, Guevara T, Eckhard U, Sola M, Potempa J, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2021 Oct 5;118(40). pii: 2103573118. doi:, 10.1073/pnas.2103573118. Epub 2021 Sep 30. PMID:34593635 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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