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

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 u...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-07, Vol.110 (29), p.E2677-E2686
Main Authors: Madasu, Yadaiah, Suarez, Cristian, Kast, David J, Kovar, David R, Dominguez, Roberto
Format: Article
Language:English
Subjects:
actin
Actins - metabolism
antigens
Antigens, Bacterial - chemistry
Antigens, Bacterial - metabolism
bacterial proteins
Bacterial Proteins - chemistry
Bacterial Proteins - metabolism
Biological Sciences
Calorimetry
Circular Dichroism
Crystal structure
Crystallization
Eukaryotes
Evolution, Molecular
Fetal Proteins - metabolism
Gram-negative bacteria
Microfilament Proteins - chemistry
Microfilament Proteins - metabolism
Microscopy, Fluorescence
Models, Molecular
Molecules
Nuclear Proteins - metabolism
PNAS Plus
Profilins - metabolism
Protein Conformation
Protein Structure, Tertiary
Proteins
Rickettsia
Rickettsia - genetics
Terminal Repeat Sequences - genetics
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Summary: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 α-helical fold is unusual among Gram-negative autotransporters, which overwhelmingly fold as β-solenoids. Rickettsia has therefore “rediscovered” formin-like actin nucleation and elongation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1307235110