1,721,128 research outputs found
Structural and functional aspects of the Helicobacter pylori secretome
No full textProteins secreted by Helicobacter pylori (H. pylori ),
an important human pathogen responsible for severe
gastric diseases, are reviewed from the point of view
of their biochemical characterization, both functional
and structural. Despite the vast amount of experimental
data available on the proteins secreted by this
bacterium, the precise size of the secretome remains
unknown. In this review, we consider as secreted
both proteins that contain a secretion signal for the
periplasm and proteins that have been detected in the
external medium in in vitro experiments. In this way, H.
pylori ’s secretome appears to be composed of slightly
more than 160 proteins, but this number must be considered
very cautiously, not only because the definition
of secretome itself is ambiguous but also because the
included proteins were observed as secreted in in vitro
experiments that were not representative of the environmental
situation in vivo . The proteins that appear
to be secreted can be grouped into different classes:
enzymes (48 proteins), outer membrane proteins (43),
components of flagella (11), members of the cytotoxicassociated
genes pathogenicity island or other toxins
(8 and 5, respectively), binding and transport proteins
(9), and others (11). A final group, which includes 28
members, is represented by hypothetical uncharacterized
proteins. Despite the large amount of data accumulated
on the H. pylori secretome, a considerable
amount of work remains to reach a full comprehension
of the system at the molecular level
Crystal structure of the [FeFe]-Hydrogenase maturation protein HYDF reveals new insights into the H-cluster biosynthetic scaffold
No full textStructural and functional studies on the Helicobacter pylori proteome: the state of the art
No full textHelicobacter pylori, cag pathogenicity Island, crystallography, protein structures
Structural and functional aspects of Helicobacter pylori acidic stress response factors
No full textHelicobacter pylori is a striking example of adaptation of a
bacterium to a very peculiar niche, the human stomach. Despite
being a neutralophile, a sophisticated control of gene expression
allows it to live and to proliferate in an environment that cycles
from nearly neutral to very acidic. Despite the numerous studies
performed on the mechanisms of acid adaptation, the physiological
function of a large part of the genes products that are
up-regulated or down-regulated is often not clear, in particular
in the context of the response of the bacterium to an acidic
stress. In this review, we discuss the molecular and functional
aspects of some of the proteins that are commonly found overexpressed
during the acid stress
Crystal structure of the secreted protein HP1454 from the human pathogenHelicobacter pylori
No full textHP1454 is a protein of 303 amino acids found in the extracellular milieu of Helicobacter pylori. The protein structure, crystallized in the orthorhombic C2221 space group with one molecule per asymmetric unit, has been determined using the single-wavelength anomalous dispersion method. HP1454 exhibits an elongated bent shape, composed of three distinct domains. Each domain possesses a fold already present in other structures: Domain I contains a three-strand antiparallel β-barrel flanked by a long α-helix, Domain II is an anti-parallel three-helix bundle, and Domain III a β-sheet flanked by two α-helices. The overall assembly of the protein does not bear any similarity with known structures. © 2014 Wiley Periodicals, Inc
Structural and functional aspects of unique type IV secretory components in the Helicobacter pylori cag-pathogenicity island
No full textHelicobacter pylori cytotoxin-associated gene-pathogenicity island (cagPAI) is responsible for the secretion of the CagA effector through a type IV secretion system (T4SS) apparatus, as well as of peptidoglycan and possibly other not yet identified factors. Twenty-nine different polypeptide chains are encoded by this cluster of genes, although only some of them show a significant similarity with the constitutive elements of well characterized secretion systems from other bacteria. The other cagPAI components represent almost unique proteins in this scenario. The majority of the T4SS include approximately fifteen components, taking into account either the transmembrane complex subunits, ATPases or substrate factors. The composition of the cagPAI is very complex: it includes proteins most likely involved at different levels in the pilus assembly, stabilization and processing of secreted substrate, as well as regulatory particles possibly involved in the control of the entire apparatus. Despite recent findings with respect to components that play a role in the interaction with the host cell, the function of several cagPAI proteins remains unclear or unknown. This is particularly true for those that represent unique members with no clear similarity to those of other T4SS and no obvious evidence of involvement in the secretion of CagA or induction of pro-inflammatory responses. We summarize what is known about these accessory components, both from a molecular and structural point of view, as well as their putative physiological role
Structure-function relationship in multimeric snake pre-synaptic phospholipase A2 neurotoxins
No full textStructural and mutational analysis of TenA protein (HP1287) from the Helicobacter pylori thiamin salvage pathway - evidence of a different substrate specificity
No full textHP1287 (tenA) from Helicobacter pylori is included among the genes that
play a relevant role in bacterium colonization and persistence. The gene
has been cloned and its product, protein TenA, has been expressed and
purified. The crystal structures of the wild-type protein and the mutant
F47Y have been determined at resolutions of 2.7 and 2.4 A ̊ , respectively.
The molecular model, a homotetramer with 222 symmetry, shows that the
H. pylori TenA structure belongs to the thiaminase II class of proteins.
These enzymes were recently found to be involved in a salvage pathway for
the synthesis of the thiamin precursor hydroxypyrimidine, which constitutes
a building block in thiamin biosynthesis, in particular in bacteria living in
the soil. By contrast, enzymatic measurements on TenA from H. pylori
indicate that the activity on the putative substrate 4-amino-5-aminomethyl-
2-methylpyrimidine is very modest. Moreover, in the present study, we
demonstrate that the mutation at residue 47, a position where a phenylalanine
occurs in all the strains of H. pylori sequenced to date, is not sufficient
to explain the very low catalytic activity toward the expected substrate. As
a result of differences in the colonization environment of H. pylori as well
as the TenA structural and catalytic peculiar features, we suggest a possible
pivotal role for the H. pylori enzyme in the thiamin biosynthetic route,
which is in agreement with the relevance of this protein in the stomach
colonization process
Identification and characterization of a new formate dehydrogenase from the acidobacterium Granulicella mallensis MP5ACTX8
No full textHelicobacter pylori acidic stress response factor HP1286 is a YceI homolog with new binding specificity
No full textHP1286 from Helicobacter pylori is among the proteins that play a relevant
role in bacterial colonization and persistence in the stomach. Indeed, it was
demonstrated to be overexpressed under acidic stress conditions, together
with other essential virulence factors. Here we describe its crystal structure,
determined at 2.1 A ̊ resolution. The molecular model, a dimer characterized
by two-fold symmetry, shows that HP1286 structurally belongs to the YceIlike
protein family, which in turn is characterized by the lipocalin fold. The
latter characterizes proteins possessing an internal cavity with the function of
binding and ⁄ or transport of amphiphilic molecules. Surprisingly, a molecule
of erucamide was found bound in the internal cavity of each monomer of
recombinant HP1286, cloned and expressed in an Escherichia coli heterologous
system. The shape and length of the cavity indicate that, at variance
with other members of the family, HP-YceI has a binding specificity for
amphiphilic compounds with a linear chain of about 22 carbon atoms. These
features, along with the fact that the protein is secreted by the bacterium and
is involved in adaptation to an acidic environment, suggest that its function
could be that of sequestering specific fatty acids or amides from the environment,
either to supply the bacterium with the fatty acids necessary for its
metabolism, or to protect and detoxify it from the detergent-like antimicrobial
activity of fatty acids that are eventually present in the external milieu
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