9DCS
Structure of a TelD-associated type VII secretion system DUF4176 protein
Summary for 9DCS
| Entry DOI | 10.2210/pdb9dcs/pdb |
| Descriptor | DUF4176 domain-containing protein, FORMIC ACID, ACETIC ACID, ... (4 entities in total) |
| Functional Keywords | molecular chaperone, type vii secretion system, antibacterial toxins, chaperone |
| Biological source | Streptococcus intermedius |
| Total number of polymer chains | 4 |
| Total formula weight | 49040.19 |
| Authors | |
| Primary citation | Gkragkopoulou, P.,Garrett, S.R.,Shah, P.Y.,Grebenc, D.W.,Klein, T.A.,Kim, Y.,Whitney, J.C. A widespread family of molecular chaperones promotes the intracellular stability of type VIIb secretion system-exported toxins. Proc.Natl.Acad.Sci.USA, 122:e2503581122-e2503581122, 2025 Cited by PubMed Abstract: To survive in highly competitive environments, bacteria use specialized secretion systems to deliver antibacterial toxins into neighboring cells, thereby inhibiting their growth. In many Gram-positive bacteria, the export of such toxins requires a membrane-bound molecular apparatus known as the type VIIb secretion system (T7SSb). Recently, it was shown that toxin recruitment to the T7SSb requires a physical interaction between a toxin and two or more so-called targeting factors, which harbor key residues required for T7SS-dependent protein export. However, in addition to these targeting factors, some toxins additionally require a protein belonging to the DUF4176 protein family. Here, by examining two toxin-DUF4176 protein pairs, we demonstrate that DUF4176 constitutes a family of toxin-specific molecular chaperones. In addition to being required for toxin stability in producing cells, we find that DUF4176 proteins facilitate toxin export by specifically interacting with a previously uncharacterized intrinsically disordered region found in many T7SS toxins. Using X-ray crystallography, we determine structures of several DUF4176 chaperones in their unbound state, and of a DUF4176 chaperone in complex with the binding site of its cognate toxin. These structures reveal that this binding site consists of a disordered amphipathic α-helix that requires interaction with its cognate chaperone for proper folding. Overall, we have identified a family of secretion system associated molecular chaperones found throughout T7SSb-containing Gram-positive bacteria. PubMed: 40953262DOI: 10.1073/pnas.2503581122 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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