title: Crystal structures of a polypeptide processing and secretion transporter.
abstract: Bacteria secrete peptides and proteins to communicate, to poison competitors, and to manipulate host cells. Among the various protein-translocation machineries, the peptidase-containing ATP-binding cassette transporters (PCATs) are appealingly simple. Each PCAT contains two peptidase domains that cleave the secretion signal from the substrate, two transmembrane domains that form a translocation pathway, and two nucleotide-binding domains that hydrolyse ATP. In Gram-positive bacteria, PCATs function both as maturation proteases and exporters for quorum-sensing or antimicrobial polypeptides. In Gram-negative bacteria, PCATs interact with two other membrane proteins to form the type 1 secretion system. Here we present crystal structures of PCAT1 from Clostridium thermocellum in two different conformations. These structures, accompanied by biochemical data, show that the translocation pathway is a large α-helical barrel sufficient to accommodate small folded proteins. ATP binding alternates access to the transmembrane pathway and also regulates the protease activity, thereby coupling substrate processing to translocation.
authors.affiliation: 1] Laboratory of Membrane Biology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: David Yin-wei
authors.initials: DY
authors.lastname: Lin
authors.affiliation: Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: 1] Laboratory of Membrane Biology and Biophysics, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Chen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000172:deficiency / Q000378:metabolism; D048013:Acetivibrio thermocellus / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D018528:ATP-Binding Cassette Transporters; D010455:Peptides; D000255:Adenosine Triphosphate