9DCT

Structure of the TelB-associated type VII secretion system chaperone SIR_0178

9DCT の概要

• エントリーDOI: 10.2210/pdb9dct/pdb
• 分子名称: DUF4176 domain-containing protein, CHLORIDE ION (2 entities in total)
• 機能のキーワード: molecular chaperone, type vii secretion system, antibacterial toxins, chaperone
• 由来する生物種: Streptococcus intermedius B196
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 115523.23

構造登録者

Gkragkopoulou, P.,Kim, Y.,Whitney, J.C. (登録日: 2024-08-27, 公開日: 2025-11-05)

主引用文献

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

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: 40953262
DOI: 10.1073/pnas.2503581122

実験手法

X-RAY DIFFRACTION (3.24 Å)