Transformer Proteins!

Few proteins can transform their domain structure from one secondary structural form to another, say for example from alpha to beta upon a suitable stimulus. What is interesting is that the same protein that has transformed into two distinct structures accomplish entirely two different functions in bacteria – a protein pleiotropism!?

Gene expression starts with Transcription. The transcription process is a cyclic event consisting of three major steps: initiation, elongation, and termination. The enzyme RNA polymerase (RNAP), is responsible for the starting step in gene expression, the mRNA synthesis.

Recent studies show the fact that RNA polymerase, the enzyme that transcribes DNA into RNA, is a target for numerous regulatory events in all living cells.

The RfaH protein is a bacterial elongation factor, involved in Transcription. During transcription, RfaH remains bound to the enzyme, RNA polymerase (RNAP) and acts as an antiterminator by reducing two important processes,  pausing and termination.  Irina Artsimovitch of Ohio State University solved the structure of RfaH Protein in 2007.

Irina Artsimovitch along with Paul Rösch and Artsimovitch’s team at the University of Bayreuth made an interesting discovery recently.

Their studies in the most common micro flora of the gut, Escherichia coli, lead to the discovery that RfaH protein is made-up of two distinct domains connected by a flexible linker - a C-terminal half of the RfaH protein that resembles nunchucks (apha-hairpin-alpha) and an amino-terminal domain (N-Terminal Domain, NTD) that recognizes and binds to the RNA polymerase which is essential for the transcription process.

The two domains are closely associated initially. During transcription initiation, the binding of the NTD of RfaH to DNA leads to a spatial separation of the two domains (CTD and NTD). This acts as a signal for a structural switch CTD of the RfaH protein. The structural switch results in a complete structural rearrangement of the CTD structure from the alpha helical hairpin into a fold that completely different beta barrel structure.

Now, the β-barrel domain recruits ribosome and help in the translation process of the transcribed product.

This transforming ability in the structure allows this RfaH protein to physically couple the processes of transcription and translation in gene expression.

The change in the structure of the RfaH protein happens to turn on those genes that give E. coli its ability to infect.

-         Dr. P. Kumarasamy