The Chlamydia pneumoniae Adhesin Pmp21 Forms Oligomers with Adhesive Properties.

Autor:	Luczak SE; From the Institute of Functional Microbial Genomics., Smits SH; Institute of Biochemistry, and., Decker C; Institute of Physical Biology, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany and., Nagel-Steger L; Institute of Physical Biology, Heinrich-Heine-University, Universitaetsstrasse 1, 40225 Duesseldorf, Germany and.; ICS-6 Research Center Juelich, 52425 Juelich, Germany., Schmitt L; Institute of Biochemistry, and., Hegemann JH; From the Institute of Functional Microbial Genomics, Johannes.hegemann@hhu.de.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2016 Oct 21; Vol. 291 (43), pp. 22806-22818. Date of Electronic Publication: 2016 Aug 22.
DOI:	10.1074/jbc.M116.728915
Abstrakt:	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. (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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