Molecular Playground/Homo-dimeric RcdA

Introduction

RcdA was first identified as a regulator for the degradation of CtrA, a master regulator in Caulobacter crescentus (McGrath et al., 2006). It was shown to facilitate the degradation of CtrA during swarmer to stalked transition of Caulobacter life cycle. In 2009, its crystal structure was solved at a resolution of 2.9 A (Taylor et al., 2009). However, to date, the details of the precise function and mechanism of RcdA are unclear. We, at the Chien lab are working towards understanding the role of RcdA in regulated proteolysis of different key regulators in the model organism Caulobacter [[1]]

Biological state of RcdA

RcdA exists as a homodimer in solution. This has been shown by size exclusion chromatography and has been further supported by the analysis of its crystal structure (Taylor et al., 2009). The monomeric unit of RcdA consists of a three-helix bundle with three disordered regions. Both monomeric units pack each other in a 2-fold symmetric orientation. The monomeric subunits are shown in red and blue in the figure.

Conservation of RcdA

RcdA is generally conserved across gram-negative alpha-proteobacteria. This suggests that RcdA might play an important role in the regulatory processes of Caulobacter. The conservation of different residues as predicted by Consurf software is shown in the diagram at the right. Clearly residues are more conserved at the dimer interface than on the surface of the protein, indicating that dimerization might be key for functionality. The color scheme representing the conservation scores is shown below.

References: 1. Patrick T. McGrath, Antonio A. Iniesta, Kathleen R. Ryan, Lucy Shapiro and Harley H. McAdams. " A Dynamically Localized Protease Complex and a Polar Specificity Factor Control a Cell Cycle Master Regulator". Cell, (2006) 124, 535–547. 2. James A. Taylor, Jeremy D. Wilbur, Stephen C. Smith and Kathleen R. Ryan. "Mutations that Alter RcdA Surface Residues Decouple Protein Localization and CtrA Proteolysis in Caulobacter crescentus". J. Mol. Biol. (2009) 394,46–60.