User:Chloe Paul/Replication Terminator Protein: Difference between revisions

<StructureSection load='2efw' size='300' side='right' caption='RTP bound to native DNA (PDB entry [[2efw]])' scene='User:Chloe_Paul/Replication_Terminator_Protein/Rtpasym/3'>The RTP:DNA interaction has been shown to be able to induce two different conformations of RTP depending upon the nature of the DNA. Early experiments used to determine how they interacted, used symmetric DNA (sDNA) which resulted in RTP binding symmetrically. However in nature, RTP was found to have a polar mechanism which implied asymmetric binding, leading to further investigations of how RTP bound to DNA. It was later shown that when RTP bound to native or non-symmetric DNA (nDNA) it induced an asymmetric "wing-up, wing-down" form of RTP<ref name="vivian" />.

As previously noted the role of RTP is to terminate replication of the bacterial chromosome. It was originally assumed that the role of RTP was simply to arrest the replication fork allowing the DNA to cleanly separate <ref name=“wake”>PMID: 9271849</ref>. The proposed mechanism noted that the replication fork is only able to disrupt the RTP/Ter interaction when approaching the A-site/"blocking face". The directionality of the Ter sites (ie. the orientation of A site vs B site) will determine from which direction replication will be arrested. However recent research has indicated a more complex mechanism involving interactions between bound RTP and the replication fork helicase. The results of this research have confirmed a RTP/DnaB interaction in vivo, further suggesting this interaction plays an important role in replication fork arrest <ref name=“gautam”>PMID:11124956</ref>. This has lead to the development of a new helicase-specific model involving protein-protein interactions between the replication fork helicase and RTP protein which arrests the replication fork when it approaches from the appropriate direction <ref name=“kaplan”>PMID:19298368</ref>. This evidence allows us to move from a simple "fork arrest model" to a more complex understanding of termination.

RTP is frequently compared to Termination Utilisation Sequence (Tus) from E. coli. These two proteins display similar intracellular function with binding to Ter sites resulting in replication termination, despite the significant lack of identity and similarity between them (22% identity, 44% similarity)<ref name="bussiere" />. Structurally these proteins differ as Tus has been demonstrated to be a monomer and an additional 300kbp larger than RTP<ref name="bussiere" />. Investigations into their comparative function have shown that the substitution of RTP for Tus in the E.coli system, will demonstrate no phenotypic difference, and hence share the same function as replication terminators. However the question still remains to be answered how can two structurally different proteins give rise to the same intracellular function. Hopefully, further investigations will be able to shed more light as to how RTP and Tus, from B. subtilis and E. coli respecively, arrest the replication fork mechanism.