title: Structural determinants of protein translocation in bacteria: conformational flexibility of SecA IRA1 loop region.
abstract: Bacteria employ the SecA motor protein to push unfolded proteins across the cytoplasmic membrane through the SecY protein-conducting channel complex. The crystal structure of the SecA-SecY complex shows that the intramolecular regulator of ATPase1 (IRA1) SecA domain, made up of two helices and the loop between them, is partly inserted into the SecY conducting channel, with the loop between the helices as the main functional region. A computational analysis suggested that the entire IRA1 domain is structurally autonomous, and was the basis to synthesize peptide analogs of the SecA IRA1 loop region, to the aim of investigating its conformational preferences. Our study indicates that the loop region populates a predominantly flexible state, even in the presence of structuring agent. This provides indirect evidence that the SecA loop-SecY receptor docking involves loop-mediated opening of the SecY channel.
authors.affiliation: Dipartimento delle Scienze Biologiche and CIRPeB, Università degli Studi Federico II, Naples, Italy. pasquale.palladino@unina.it
authors.forename: Pasquale
authors.initials: P
authors.lastname: Palladino
authors.forename: Gabriella
authors.initials: G
authors.lastname: Saviano
authors.forename: Teodorico
authors.initials: T
authors.lastname: Tancredi
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ragone
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D021381:Protein Transport; D000069816:SEC Translocation Channels; D000081416:SecA Proteins
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; C057841:SecY protein, E coli; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins