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TitleStabilization of F-actin by Salmonella effector SipA resembles the structural effects of inorganic phosphate and phalloidin.
Journal, issue, pagesStructure, Vol. 32, Issue 6, Page 725-738.e8, Year 2024
Publish dateJun 6, 2024
AuthorsEwa Niedzialkowska / Lucas A Runyan / Elena Kudryashova / Edward H Egelman / Dmitri S Kudryashov /
PubMed AbstractEntry of Salmonella into host enterocytes relies on its pathogenicity island 1 effector SipA. We found that SipA binds to F-actin in a 1:2 stoichiometry with sub-nanomolar affinity. A cryo-EM ...Entry of Salmonella into host enterocytes relies on its pathogenicity island 1 effector SipA. We found that SipA binds to F-actin in a 1:2 stoichiometry with sub-nanomolar affinity. A cryo-EM reconstruction revealed that SipA's globular core binds at the groove between actin strands, whereas the extended C-terminal arm penetrates deeply into the inter-strand space, stabilizing F-actin from within. The unusually strong binding of SipA is achieved by a combination of fast association via the core and very slow dissociation dictated by the arm. Similar to P, BeF, and phalloidin, SipA potently inhibited actin depolymerization by actin depolymerizing factor (ADF)/cofilin, which correlated with increased filament stiffness, supporting the hypothesis that F-actin's mechanical properties contribute to the recognition of its nucleotide state by protein partners. The remarkably strong binding to F-actin maximizes the toxin's effects at the injection site while minimizing global influence on the cytoskeleton and preventing pathogen detection by the host cell.
External linksStructure / PubMed:38518780 / PubMed Central
MethodsEM (helical sym.)
Resolution3.2 Å
Structure data

42161

8uee

EMDB-42161, PDB-8uee:
Atomic structure of Salmonella SipA/F-actin complex by cryo-EM
Method: EM (helical sym.) / Resolution: 3.2 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-PO4:
PHOSPHATE ION

ChemComp-HOH:
WATER

Source
  • oryctolagus cuniculus (rabbit)
  • salmonella enterica subsp. enterica serovar typhimurium str. lt2 (bacteria)
KeywordsCELL INVASION / actin / Salmonella / type III secretion system / SipA

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