title: Transformation: the next level of regulation.
abstract: The textbook view that a primary sequence determines the unique fold of a given protein has been challenged by identification of proteins with variant structures, such as prions. Our recent studies revealed that the transcription factor RfaH simultaneously changes its topology and function. RfaH is a two-domain protein whose N-terminal domain binds to transcribing RNA polymerase, stimulating its processivity. The α-helical C-terminal domain masks the RNA polymerase-binding site of the N-terminal domain, preventing unwarranted recruitment to genes lacking a specific DNA sequence. Upon binding to its DNA target, RfaH domains dissociate, and the C-terminal domain refolds into a β-barrel. This dramatic transformation allows binding to the ribosomal protein S10 and subsequent recruitment of a ribosome, coupling transcription and translation. We define RfaH as first example of "transformer proteins", in which two alternative structural states have distinct cellular functions and hypothesize that transformer proteins may be widespread in nature.
authors.affiliation: Lehrstuhl Biopolymere und Forschungszentrum für Bio-Makromoleküle, Universität Bayreuth, Bayreuth, Germany. artsimovitch.1@osu.edu
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Knauer
authors.forename: Paul
authors.initials: P
authors.lastname: Rösch
authors.forename: Irina
authors.initials: I
authors.lastname: Artsimovitch
mesh_terms: D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014170:Transformation, Genetic
chemical_list: D029968:Escherichia coli Proteins; C070291:NusG protein, E coli; D010445:Peptide Elongation Factors; D012329:RNA, Bacterial; D012333:RNA, Messenger; C106401:RfaH protein, E coli; D012269:Ribosomal Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D012321:DNA-Directed RNA Polymerases
keywords: NusG; RfaH; metamorphic protein; moonlighting protein; multifunctionality; opsDNA; protein folding; refolding; transcription factor; transformer protein