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@ARTICLE{Luczak:827031,
author = {Luczak, Sören E. T. and Smits, Sander H. J. and Decker,
Christina and Nagel-Steger, Luitgard and Schmitt, Lutz and
Hegemann, Johannes H.},
title = {{T}he {C}hlamydia pneumoniae {A}dhesin {P}mp21 {F}orms
{O}ligomers with {A}dhesive {P}roperties},
journal = {The journal of biological chemistry},
volume = {291},
number = {43},
issn = {0021-9258},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {FZJ-2017-01237},
pages = {22806-22818},
year = {2016},
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.},
cin = {ICS-6},
ddc = {570},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000386760600037},
pubmed = {pmid:27551038},
doi = {10.1074/jbc.M116.728915},
url = {https://juser.fz-juelich.de/record/827031},
}