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Predicting the Complex Structure and Functional Motions of the Outer Membrane Transporter and Signal Transducer FecA

Taner Z. Sen ^* , Margaret Kloster ^*, Robert L. Jernigan ^* , Andrzej Kolinski , Janusz M. Bujnicki  ^¶ and Andrzej Kloczkowski ^* 

^* L. H. Baker Center for Bioinformatics and Biological Statistics, Iowa State University, Ames, Iowa; Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa; Faculty of Chemistry, Warsaw University, Warsaw, Poland; Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Warsaw, Poland; and ^¶ Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland

Correspondence: Address reprint requests to Taner Z. Sen, USDA-ARS Corn Insects and Crop Genetics Research Unit, Ames, IA 50011-3260; or Dept. of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011-3260. Tel.: 515-294-4294; E-mail: taner{at}iastate.edu.

Escherichia coli requires an efficient transport and signaling system to successfully sequester iron from its environment. FecA, a TonB-dependent protein, serves a critical role in this process: first, it binds and transports iron in the form of ferric citrate, and second, it initiates a signaling cascade that results in the transcription of several iron transporter genes in interaction with inner membrane proteins. The structure of the plug and barrel domains and the periplasmic N-terminal domain (NTD) are separately available. However, the linker connecting the plug and barrel and the NTD domains is highly mobile, which may prevent the determination of the FecA structure as a whole assembly. Here, we reduce the conformation space of this linker into most probable structural models using the modeling tool CABS, then apply normal-mode analysis to investigate the motions of the whole structure of FecA by using elastic network models. We relate the FecA domain motions to the outer-inner membrane communication, which initiates transcription. We observe that the global motions of FecA assign flexibility to the TonB box and the NTD, and control the exposure of the TonB box for binding to the TonB inner membrane protein, suggesting how these motions relate to FecA function. Our simulations suggest the presence of a communication between the loops on both ends of the protein, a signaling mechanism by which a signal could be transmitted by conformational transitions in response to the binding of ferric citrate.