Towards structure of HelD – a partner protein of RNAp in gram positive bacteria

J. Dohnálek1, T. Kovaľ1, M. Trundová,1 J. Wiedermannová2, P. Sudzinová,2 A. Rabatinová,2 H. Šanderová,2 O. Ramaniuk,2 Š. Rittich, P. Halada,2 L. Krásný2

1Institute of Biotechnology CAS, v.v.i., Biocev, Průmyslová 595, Vestec, 252 42 Jesenice u Prahy, Czech Republic

2Institute of Microbiology CAS, v. v. i., Vídeňská 1083, 14220 Praha 4, Czech Republic

dohnalek@ibt.cas.cz

The multisubunit protein complex - bacterial RNA polymerase - employs a protein partner called HelD. We have characterised this protein from Bacillus subtilis (1, 2). HelD stimulates transcription in an ATP-dependent manner by enhancing transcriptional cycling and elongation. Its effect can be amplified by subunit delta. Based on sequence homology HelD belongs to the superfamily of DNA and RNA helicases, possesses an ATP binding cassette but its structure and molecular detail of function cannot be easily inferred from the knowledge about the model helicases UvrD and Rep from E. coli. HelD interacts with the RNAP core between the secondary channel of RNAP and the alpha subunits and is highly likely capable of DNA/RNA binding. We have extensively studied the role of HelD in transcription initiation and elongation, its biophysical properties, sequence and domain structure and co-stimulatory effects (2).

In our effort to gain insights into the structure-function relationship of this RNAp partner we have recently cloned, expresed and purified several homologs from other organisms – Bacillus atrophaeus, Geobacillus stearothermophillus and Mycobacterium smegmatis. Biophysical characterisation and initial SAXS experiments help optimize these targets for further structural studies.

1. O. Delumeau, F. Lecointe, J. Muntel, et al., Proteomics, 2011, 11, 2992–3001.

2.  J. Wiedermannova, P. Sudzinova, H. Sanderova, et al., Nucleic Acids Res., 2014, 42, 5151-5163.

This work is supported by the project „BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University (CZ.1.05/1.1.00/02.0109), from the ERDF and by the Czech Science Foundation (grant No. 15-05228S).