Rickettsia sca2 has evolved formin-like activity through a different molecular mechanism

Yadaiah Madasu, Cristian Suarez, David J. Kast, David R. Kovar, Roberto Dominguez

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Sca2 (surface cell antigen 2) is the only bacterial protein known to promote both actin filament nucleation and profilin-dependent elongation, mimicking eukaryotic formins to assemble actin comet tails for Rickettsia motility. We show that Sca2's functional mimicry of formins is achieved through a unique mechanism. Unlike formins, Sca2 is monomeric, but has N- and C-terminal repeat domains (NRD and CRD) that interact with each other for processive barbed-end elongation. The crystal structure of NRD reveals a previously undescribed fold, consisting of helix-loop-helix repeats arranged into an overall crescent shape. CRD is predicted to share this fold and might form together with NRD, a doughnut-shaped formin-like structure. In between NRD and CRD, proline-rich sequences mediate the incorporation of profilin-Actin for elongation, and WASP-homology 2 (WH2) domains recruit actin monomers for nucleation. Sca2's a-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as β-solenoids. Rickettsia has therefore 'rediscovered' formin-like actin nucleation and elongation.

Original languageEnglish
Pages (from-to)E2677-E2686
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number29
DOIs
StatePublished - Jul 16 2013

Keywords

  • Passenger domain
  • Spotted fever
  • Translocator domain

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