Crystal structures of a polypeptide processing and secretion transporter.
Publication Type:
Journal ArticleSource:
Nature, Volume 523, Issue 7561, p.425-30 (2015)Keywords:
Adenosine Triphosphate, ATP-Binding Cassette Transporters, Clostridium thermocellum, Crystallography, X-Ray, Models, Molecular, Peptides, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Structure-Activity RelationshipAbstract:
<p>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. </p>