title: Dimeric Structure of the Bacterial Extracellular Foldase PrsA.
abstract: Secretion of proteins into the membrane-cell wall space is essential for cell wall biosynthesis and pathogenicity in Gram-positive bacteria. Folding and maturation of many secreted proteins depend on a single extracellular foldase, the PrsA protein. PrsA is a 30-kDa protein, lipid anchored to the outer leaflet of the cell membrane. The crystal structure of Bacillus subtilis PrsA reveals a central catalytic parvulin-type prolyl isomerase domain, which is inserted into a larger composite NC domain formed by the N- and C-terminal regions. This domain architecture resembles, despite a lack of sequence conservation, both trigger factor, a ribosome-binding bacterial chaperone, and SurA, a periplasmic chaperone in Gram-negative bacteria. Two main structural differences are observed in that the N-terminal arm of PrsA is substantially shortened relative to the trigger factor and SurA and in that PrsA is found to dimerize in a unique fashion via its NC domain. Dimerization leads to a large, bowl-shaped crevice, which might be involved in vivo in protecting substrate proteins from aggregation. NMR experiments reveal a direct, dynamic interaction of both the parvulin and the NC domain with secretion propeptides, which have been implicated in substrate targeting to PrsA.
authors.affiliation: From the Biozentrum, Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland and roman.jakob@unibas.ch.
authors.forename: Roman P
authors.initials: RP
authors.lastname: Jakob
authors.affiliation: the Laboratorium für Biochemie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Johanna R
authors.initials: JR
authors.lastname: Koch
authors.affiliation: From the Biozentrum, Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland and.
authors.forename: Björn M
authors.initials: BM
authors.lastname: Burmann
authors.affiliation: the Laboratorium für Biochemie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Philipp A M
authors.initials: PA
authors.lastname: Schmidpeter
authors.affiliation: From the Biozentrum, Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland and.
authors.forename: Moritz
authors.initials: M
authors.lastname: Hunkeler
authors.affiliation: From the Biozentrum, Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland and.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hiller
authors.affiliation: the Laboratorium für Biochemie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Schmid
authors.affiliation: From the Biozentrum, Universität Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland and timm.maier@unibas.ch.
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D055503:Protein Multimerization
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins; D008565:Membrane Proteins; C082160:prsA protein, bacteria
keywords: Biophysics; Cell Wall; Chaperone; Gram-positive Bacteria; Prolyl Isomerase; Protein Folding; Protein Secretion; X-ray Crystallography