title: The non-penicillin-binding module of the tripartite penicillin-binding protein 3 of Escherichia coli is required for folding and/or stability of the penicillin-binding module and the membrane-anchoring module confers cell septation activity on the folded structure.
abstract: The ftsI-encoded multimodular class B penicillin-binding protein 3 (PBP3) is a key element of the cell septation machinery of Escherichia coli. Altered ftsI genes were overexpressed, and the gene products were analyzed with respect to the level of production, stability, penicillin affinity, and cell septation activity. In contrast to the serine beta-lactamases and low-molecular-mass PBPs which are autonomous folding entities, the S-259-to-V-577 penicillin-binding module of M-1-to-V-577 PBP3 lacks the amino acid sequence information for correct folding. The missing piece of information is provided by the associated G-57-to-E-258 non-penicillin-binding module which functions as a noncleaved, pseudointramolecular chaperone. Key elements of the folding information reside within the motif 1-containing R-60-to-W-110 polypeptide segment and within G-188-to-D-197 motif 3 of the n-PB module. The intermodule interaction is discussed in the light of the known three-dimensional structure (at 3.5-A [0.35-nm] resolution) of the analogous class B PBP2x of Streptococcus pneumoniae (S. Pares, N. Mouz, Y. Pétillot, R. Hakenbeck, and O. Dideberg, Nature Struct. Biol. 3:284-289, 1996). Correct folding and adoption of a stable penicillin-binding conformation are necessary but not sufficient to confer cell septation activity to PBP3 in exponentially growing cells. The in vivo activity of PBP3 also depends on the M-1-to-E-56 amino-terminal module which encompasses the cytosol, the membrane, and the periplasm and which functions as a noncleaved pseudo-signal peptide.
authors.affiliation: Centre d'Ingénierie des Protéines, Université de Liège, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Goffin
authors.forename: C
authors.initials: C
authors.lastname: Fraipont
authors.forename: J
authors.initials: J
authors.lastname: Ayala
authors.forename: M
authors.initials: M
authors.lastname: Terrak
authors.forename: M
authors.initials: M
authors.lastname: Nguyen-Distèche
authors.forename: J M
authors.initials: JM
authors.lastname: Ghuysen
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D002352:Carrier Proteins; D002455:Cell Division; D004795:Enzyme Stability; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D002267:Muramoylpentapeptide Carboxypeptidase; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; D010458:Peptidyl Transferases / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014170:Transformation, Genetic
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C478704:FtsI protein, E coli; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D046915:Penicillin-Binding Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; D005982:Glutathione Transferase; D002267:Muramoylpentapeptide Carboxypeptidase