title: The Chlamydia pneumoniae Adhesin Pmp21 Forms Oligomers with Adhesive Properties.
abstract: Chlamydiae sp. are obligate intracellular pathogens that cause a variety of diseases in humans. The adhesion of Chlamydiae to the eukaryotic host cell is a pivotal step in pathogenesis. The adhesin family of polymorphic membrane proteins (Pmp) in Chlamydia pneumoniae consists of 21 members. Pmp21 binds to the epidermal growth factor receptor (EGFR). Pmps contain large numbers of FXXN (where X is any amino acid) and GGA(I/L/V) motifs. At least two of these motifs are crucial for adhesion by certain Pmp21 fragments. Here we describe how the two FXXN motifs in Pmp21-D (D-Wt), a domain of Pmp21, influence its self-interaction, folding, and adhesive capacities. Refolded D-Wt molecules form oligomers with high sedimentation values (8-85 S). These oligomers take the form of elongated protofibrils, which exhibit Thioflavin T fluorescence, like the amyloid protein fragment β42. A mutant version of Pmp21-D (D-Mt), with FXXN motifs replaced by SXXV, shows a markedly reduced capacity to form oligomers. Secondary-structure assays revealed that monomers of both variants exist predominantly as random coils, whereas the oligomers form predominantly β-sheets. Adhesion studies revealed that oligomers of D-Wt (D-Wt-O) mediate significantly enhanced binding to human epithelial cells relative to D-Mt-O and monomeric protein species. Moreover, D-Wt-O binds EGFR more efficiently than D-Wt monomers. Importantly, pretreatment of human cells with D-Wt-O reduces infectivity upon subsequent challenge with C. pneumoniae more effectively than all other protein species. Hence, the FXXN motif in D-Wt induces the formation of β-sheet-rich oligomeric protofibrils, which are important for adhesion to, and subsequent infection of human cells.
authors.affiliation: From the Institute of Functional Microbial Genomics.
authors.forename: Sören E T
authors.initials: SE
authors.lastname: Luczak
authors.affiliation: Institute of Biochemistry, and.
authors.forename: Sander H J
authors.initials: SH
authors.lastname: Smits
authors.affiliation: Institute of Physical Biology, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany and.
authors.forename: Christina
authors.initials: C
authors.lastname: Decker
authors.affiliation: Institute of Physical Biology, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany and.|ICS-6 Research Center Juelich, 52425 Juelich, Germany.
authors.forename: Luitgard
authors.initials: L
authors.lastname: Nagel-Steger
authors.affiliation: Institute of Biochemistry, and.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitt
authors.affiliation: From the Institute of Functional Microbial Genomics, Johannes.hegemann@hhu.de.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Hegemann
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016993:Chlamydophila pneumoniae / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D020125:Mutation, Missense; D011485:Protein Binding; D055503:Protein Multimerization / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; C484024:polymorphic membrane protein 21, Chlamydophila pneumoniae; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Chlamydia; Pmp; adhesin; amyloid; bacterial adhesion; oligomerization