Structural conversion of the transformer protein RfaH: new insights derived from protein structure prediction and molecular dynamics simulations

Abstract

Recent structural investigations have shown that the C-terminal domain (CTD) of the transcription factor RfaH undergoes unique structural modifications that have a profound impact into its functional properties. These modifications cause a complete change in RfaH^CTD topology that converts from an α-hairpin to a β-barrel fold. To gain insights into the determinants of this major structural conversion, we here performed computational studies (protein structure prediction and molecular dynamics simulations) on RfaH^CTD. Although these analyses, in line with literature data, suggest that the isolated RfaH^CTD has a strong preference for the β-barrel fold, they also highlight that a specific region of the protein is endowed with a chameleon conformational behavior. In particular, the Leu-rich region (residues 141–145) has a good propensity to adopt both α-helical and β-structured states. Intriguingly, in the RfaH homolog NusG, whose CTD uniquely adopts the β-barrel fold, the corresponding region is rich in residues as Val or Ile that present a strong preference for the β-structure. On this basis, we suggest that the presence of this Leu-rich element in RfaH^CTD may be responsible for the peculiar structural behavior of the domain. The analysis of the sequences of RfaH family (PfamA code PF02357) unraveled that other members potentially share the structural properties of RfaH^CTD. These observations suggest that the unusual conformational behavior of RfaH^CTD may be rare but not unique.

Keywords:

• secondary structure prediction
• conformational conversion
• molecular dynamics
• transformer proteins
• amino acid propensities

Acknowledgments

The authors thank Luca De Luca for skillful technical assistance.

Additional information

Funding

This work was financially supported by MIUR (FIRB RBRN07BMCT).