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Structural conservation, variability, and immunogenicity of the T6 backbone pilin of serotype M6 Streptococcus pyogenes.
[acute rheumatic fever]
Group
A
streptococcus
(
GAS
;
Streptococcus
pyogenes
)
is
a
Gram
-
positive
human
pathogen
that
causes
a
broad
range
of
diseases
ranging
from
acute
pharyngitis
to
the
poststreptococcal
sequelae
of
acute
rheumatic
fever
.
GAS
pili
are
highly
diverse
,
long
protein
polymers
that
extend
from
the
cell
surface
.
They
have
multiple
roles
in
infection
and
are
promising
candidates
for
vaccine
development
.
This
study
describes
the
structure
of
the
T
6
backbone
pilin
(
BP
;
Lancefield
T
-
antigen
)
from
the
important
M
6
serotype
.
The
structure
reveals
a
modular
arrangement
of
three
tandem
immunoglobulin-like
domains
,
two
with
internal
isopeptide
bonds
.
The
T
6
pilin
lysine
,
essential
for
polymerization
,
is
located
in
a
novel
VAKS
motif
that
is
structurally
homologous
to
the
canonical
YPKN
pilin
lysine
in
other
three
-
and
four
-domain
Gram
-
positive
pilins
.
The
T
6
structure
also
highlights
a
conserved
pilin
core
whose
surface
is
decorated
with
highly
variable
loops
and
extensions
.
Comparison
to
other
Gram
-
positive
BPs
shows
that
many
of
the
largest
variable
extensions
are
found
in
conserved
locations
.
Studies
with
sera
from
patients
diagnosed
with
GAS
-associated
acute
rheumatic
fever
showed
that
each
of
the
three
T
6
domains
,
and
the
largest
of
the
variable
extensions
(
V
8
)
,
are
targeted
by
IgG
during
infection
in
vivo
.
Although
the
GAS
BP
show
large
variations
in
size
and
sequence
,
the
modular
nature
of
the
pilus
proteins
revealed
by
the
T
6
structure
may
aid
the
future
design
of
a
pilus-based
vaccine
.
Diseases
Validation
Diseases presenting
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated