title: Accommodation of profound sequence differences at the interfaces of eubacterial RNA polymerase multi-protein assembly.
abstract: Evolutionarily divergent proteins have been shown to change their interacting partners. RNA polymerase assembly is one of the rare cases which retain its component proteins in the course of evolution. This ubiquitous molecular assembly, involved in transcription, consists of four core subunits (alpha, beta, betaprime, and omega), which assemble to form the core enzyme. Remarkably, the orientation of the four subunits in the complex is conserved from prokaryotes to eukaryotes although their sequence similarity is low. We have studied how the sequence divergence of the core subunits of RNA polymerase is accommodated in the formation of the multi-molecular assembly, with special reference to eubacterial species. Analysis of domain composition and order of the core subunits in >85 eubacterial species indicates complete conservation. However, sequence analysis indicates that interface residues of alpha and omega subunits are more divergent than those of beta, betaprime, and sigma70 subunits. Although beta and betaprime are generally well-conserved, residues involved in interaction with divergent subunits are not conserved. Insertions/deletions are also observed near interacting regions even in case of the most conserved subunits, beta and betaprime. Homology modelling of three divergent RNA polymerase complexes, from Helicobacter pylori, Mycoplasma pulmonis and Onion yellows phytoplasma, indicates that insertions/deletions can be accommodated near the interface as they generally occur at the periphery. Evaluation of the modeled interfaces indicates that they are physico-chemically similar to that of the template interfaces in Thermus thermophilus, indicating that nature has evolved to retain the obligate complex in spite of substantial substitutions and insertions/deletions.
authors.forename: Lakshmipuram Seshadri
authors.initials: LS
authors.lastname: Swapna
authors.forename: Nambudiry
authors.initials: N
authors.lastname: Rekha
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan