8GMH

Crystal Structure of the ternary complex of TelA-LXG, LapA3, and LapA4

Summary for 8GMH

• Entry DOI: 10.2210/pdb8gmh/pdb
• Descriptor: LXG domain-containing protein, LapA4, LapA3, ... (5 entities in total)
• Functional Keywords: type vii secretion, protein secretion, bacterial toxin, targeting factors, signal sequence, protein binding
• Biological source: Streptococcus intermedius B196; More
• Total number of polymer chains: 6
• Total formula weight: 101979.13

Authors

Klein, T.A.,Shah, P.Y.,Gkragkopoulou, P.,Grebenc, D.W.,Kim, Y.,Whitney, J.C. (deposition date: 2023-03-25, release date: 2024-01-10, Last modification date: 2024-10-30)

Primary citation

Klein, T.A.,Shah, P.Y.,Gkragkopoulou, P.,Grebenc, D.W.,Kim, Y.,Whitney, J.C.
Structure of a tripartite protein complex that targets toxins to the type VII secretion system.
Proc.Natl.Acad.Sci.USA, 121:e2312455121-e2312455121, 2024

PubMed Abstract: Type VII secretion systems are membrane-embedded nanomachines used by Gram-positive bacteria to export effector proteins from the cytoplasm to the extracellular environment. Many of these effectors are polymorphic toxins comprised of an N-terminal Leu-x-Gly (LXG) domain of unknown function and a C-terminal toxin domain that inhibits the growth of bacterial competitors. In recent work, it was shown that LXG effectors require two cognate Lap proteins for T7SS-dependent export. Here, we present the 2.6 Å structure of the LXG domain of the TelA toxin from the opportunistic pathogen in complex with both of its cognate Lap targeting factors. The structure reveals an elongated α-helical bundle within which each Lap protein makes extensive hydrophobic contacts with either end of the LXG domain. Remarkably, despite low overall sequence identity, we identify striking structural similarity between our LXG complex and PE-PPE heterodimers exported by the distantly related ESX type VII secretion systems of Mycobacteria implying a conserved mechanism of effector export among diverse Gram-positive bacteria. Overall, our findings demonstrate that LXG domains, in conjunction with their cognate Lap targeting factors, represent a tripartite secretion signal for a widespread family of T7SS toxins.

PubMed: 38194450
DOI: 10.1073/pnas.2312455121

Experimental method

X-RAY DIFFRACTION (2.6 Å)