Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism.

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 ?-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as ?-solenoids. Rickettsia has therefore "rediscovered" formin-like actin nucleation and elongation.

SUBMITTER: Madasu Y 

PROVIDER: S-EPMC3718132 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature