A structural model of the E. coli PhoB Dimer in the transcription initiation complex

We use a Motif Binding Geometries (MBG) approach, to infer the structure of a protein complex from the database of complexes of homologous proteins taken from other contexts (such as the helix-turn-helix motif binding double stranded DNA), and demonstrate its utility on one of the more important regulatory complexes in biology, that of the RNA polymerase initiating transcription under conditions of phosphate starvation. The modeled PhoB/RNAP/σ-factor/DNA complex is stereo-chemically reasonable, has sufficient interfacial Solvent Excluded Surface Areas (SESAs) to provide adequate binding strength, is physically meaningful for transcription regulation, and is consistent with a variety of known experimental constraints.Based on a straightforward and easy to comprehend concept, "proteins and protein domains that fold similarly could interact similarly", a structural model of the PhoB dimer in the transcription initiation complex has been developed. This approach could be extended to enable structural modeling and prediction of other bio-molecular complexes. Just as models of individual proteins provide insight into molecular recognition, catalytic mechanism, and substrate specificity, models of protein complexes will provide understanding into the combinatorial rules of cellular regulation and signaling.Solving structures of complexes is inherently more difficult than solving those for individual proteins. As a result, significantly fewer structures of protein complexes than individual proteins have been determined experimentally [1]. In recent years, homology modeling [2,3] proved to be successful when the target protein has a similar sequence to proteins with known structures. However, the lack of a sufficiently large database of reference complexes makes the method unsuitable for structural modeling of protein complexes. A conceptually simple and straightforwardly applicable approach for modeling structures of bio-molecular complexes is highly desirable. When proposi