Structure of the enterococcal T4SS protein PrgL reveals unique dimerization interface in the VirB8 protein family

• Published in: Structure (London) Vol. 30; no. 6; pp. 876 - 885.e5
• Main Authors: Jäger, Franziska, Lamy, Anaïs, Sun, Wei-Sheng, Guerini, Nina, Berntsson, Ronnie P-A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 02.06.2022
• Subjects: conjugation; type 4 secretion systems; VirB8-like proteins; X-ray crystallography; X-ray crystallography; type 4 secretion systems; conjugation; VirB8-like proteins
• ISSN: 0969-2126; 1878-4186; 1878-4186
• DOI: 10.1016/j.str.2022.03.013

Multidrug-resistant bacteria pose serious problems in hospital-acquired infections (HAIs). Most antibiotic resistance genes are acquired via conjugative gene transfer, mediated by type 4 secretion systems (T4SS). Although most multidrug-resistant bacteria responsible for HAIs are of Gram-positive origin, with enterococci being major contributors, mostly Gram-negative T4SSs have been characterized. Here, we describe the structure and organization of PrgL, a core protein of the T4SS channel, encoded by the pCF10 plasmid from Enterococcus faecalis. The structure of PrgL displays similarity to VirB8 proteins of Gram-negative T4SSs. In vitro experiments show that the soluble domain alone is enough to drive both dimerization and dodecamerization, with a dimerization interface that differs from all other known VirB8-like proteins. In vivo experiments verify the importance of PrgL dimerization. Our findings provide insight into the molecular building blocks of Gram-positive T4SS, highlighting similarities but also unique features in PrgL compared to other VirB8-like proteins. [Display omitted] •Structure of pCF10 PrgL•PrgL forms dodecamers through its soluble domain•Dimer interface is needed for in vivo function Jäger et al. use X-ray crystallography to determine the structure of the VirB8-like protein PrgL from Enterococcus faecalis. PrgL has an unusual dimer interface that is important for both higher oligomerization and the in vivo function of the pCF10 type 4 secretion system.