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861.
Proline-rich antimicrobial peptides are a group of cationic host defense peptides of vertebrates and invertebrates characterized
by a high content of proline residues, often associated with arginine residues in repeated motifs. Those isolated from some
mammalian and insect species, although not evolutionarily related, use a similar mechanism to selectively kill Gram-negative
bacteria, with a low toxicity to animals. Unlike other types of antimicrobial peptides, their mode of action does not involve
the lysis of bacterial membranes but entails penetration into susceptible cells, where they then act intracellularly. Some
aspects of the transport system and cytoplasmic targets have been elucidated. These features make them attractive both as
anti-infective lead compounds and as a new class of potential cell-penetrating peptides capable of internalising membrane-impermeant
drugs into both bacterial and eukaryotic cells 相似文献
862.
Wesch D Peters C Oberg HH Pietschmann K Kabelitz D 《Cellular and molecular life sciences : CMLS》2011,68(14):2357-2370
Toll-like receptors (TLR) are pattern-recognition receptors that recognize a broad variety of structurally conserved molecules
derived from microbes. The recognition of TLR ligands functions as a primary sensor of the innate immune system, leading to
subsequent indirect activation of the adaptive immunity as well as none-immune cells. However, TLR are also expressed by several
T cell subsets, and the respective ligands can directly modulate their effector functions. The present review summarizes the
recent findings of γδ T cell modulation by TLR ligands. TLR1/2/6, 3, and 5 ligands can act directly in combination with T
cell receptor (TCR) stimulation to enhance cytokine/chemokine production of freshly isolated human γδ T cells. In contrast
to human γδ T cells, murine and bovine γδ T cells can directly respond to TLR2 ligands with increased proliferation and cytokine
production in a TCR-independent manner. Indirect stimulatory effects on IFN-γ production of human and murine γδ T cells via
TLR-ligand activated dendritic cells have been described for TLR2, 3, 4, 7, and 9 ligands. In addition, TLR3 and 7 ligands
indirectly increase tumor cell lysis by human γδ T cells, whereas ligation of TLR8 abolishes the suppressive activity of human
tumor-infiltrating Vδ1 γδ T cells on αβ T cells and dendritic cells. Taken together, these data suggest that TLR-mediated
signals received by γδ T cells enhance the initiation of adaptive immune responses during bacterial and viral infection directly
or indirectly. Moreover, TLR ligands enhance cytotoxic tumor responses of γδ T cells and regulate the suppressive capacity
of γδ T cells. 相似文献
863.
Wiring of vascular and neural networks requires precise guidance of growing blood vessels and axons, respectively, to reach
their targets during development. Both of the processes share common molecular signaling pathways. Transient receptor potential
canonical (TRPC) channels are calcium-permeable cation channels and gated via receptor- or store-operated mechanisms. Recent
studies have revealed the requirement of TRPC channels in mediating guidance cue-induced calcium influx and their essential
roles in regulating axon navigation and angiogenesis. Dissecting TRPC functions in these physiological processes may provide
therapeutic implications for suppressing pathological angiogenesis and improving nerve regeneration. 相似文献
864.
Antimicrobial agents are toxic to bacteria by a variety of mechanisms. One mechanism that is very dependent on the lipid composition of the bacterial membrane is the clustering of anionic lipid by cationic antimicrobial agents. Certain species of oligo-acyl-lysine (OAK) antimicrobial agents are particularly effective in clustering anionic lipids in mixtures mimicking the composition of bacterial membranes. The clustering of anionic lipids by certain cationic antimicrobial agents contributes to the anti-bacterial action of these agents. Bacterial membrane lipids are a determining factor, resulting in some species of bacteria being more susceptible than others. In addition, lipids can be used to increase the effectiveness of antimicrobial agents when administered in vivo. Therefore, we review some of the structures in which lipid mixtures can assemble, to more effectively be utilized as antimicrobial delivery systems. We describe in more detail the complexes formed between mixtures of lipids mimicking bacterial membranes and an OAK and their usefulness in synergizing with antibiotics to overcome bacterial multidrug resistance. 相似文献
865.
Marsango S Bonaccorsi di Patti MC Barra D Miele R 《Cellular and molecular life sciences : CMLS》2011,68(17):2919-2929
Prokineticins are proteins that regulate diverse biological processes including gastrointestinal motility, angiogenesis, circadian
rhythm, and innate immune response. Prokineticins bind two closed related G-protein coupled receptors (GPCRs), PKR1 and PKR2.
In general, these receptors act as molecular switches to relay activation to heterotrimeric G-proteins and a growing body
of evidence points to the fact that GPCRs exist as homo- or heterodimers. We show here by Western-blot analysis that PKR2
has a dimeric structure in neutrophils. By heterologous expression of PKR2 in Saccharomyces cerevisiae, we examined the mechanisms of intermolecular interaction of PKR2 dimerization. The potential involvement of three types
of mechanisms was investigated: coiled-coil, disulfide bridges, and hydrophobic interactions between transmembrane domains.
Characterization of differently deleted or site-directed PKR2 mutants suggests that dimerization proceeds through interactions
between transmembrane domains. We demonstrate that co-expressing binding-deficient and signaling-deficient forms of PKR2 can
re-establish receptor functionality, possibly through a domain-swapping mechanism. 相似文献
866.
Ann-Karin Haas Gunnar Kleinau Inna Hoyer Susanne Neumann Jens Furkert Claudia Rutz Ralf Schülein Marvin C. Gershengorn Gerd Krause 《Cellular and molecular life sciences : CMLS》2011,68(1):159-167
The thyrotropin receptor (TSHR) exhibits elevated cAMP signaling in the basal state and becomes fully activated by thyrotropin.
Previously we presented evidence that small-molecule ligands act allosterically within the transmembrane region in contrast
to the orthosteric extracellular hormone-binding sites. Our goal in this study was to identify positions that surround the
allosteric pocket and that are sensitive for inactivation of TSHR. Homology modeling combined with site-directed mutagenesis
and functional characterization revealed seven mutants located in the allosteric binding site that led to a decrease of basal
cAMP signaling activity. The majority of these silencing mutations, which constrain the TSHR in an inactive conformation,
are found in two clusters when mapped onto the 3D structural model. We suggest that the amino acid positions identified herein
are indicating locations where small-molecule antagonists, both neutral antagonists and inverse agonists, might interfere
with active TSHR conformations. 相似文献
867.
Montuori N Bifulco K Carriero MV La Penna C Visconte V Alfano D Pesapane A Rossi FW Salzano S Rossi G Ragno P 《Cellular and molecular life sciences : CMLS》2011,68(14):2453-2467
The receptor (CXCR4) for the stromal-derived factor-1 (SDF1) and the urokinase-receptor (uPAR) are up-regulated in various tumors. We show that CXCR4-transfected cells migrate toward SDF1 on collagen (CG) and do not on vitronectin (VN). Co-expression of cell-surface uPAR, which is a VN receptor, impairs SDF1-induced migration on CG and allows migration on VN. Blocking fMLP receptors (fMLP-R), alpha-v integrins or the uPAR region capable to interact with fMLP-Rs, impairs migration of uPAR/CXCR4-transfected cells on VN and restores their migration on CG. uPAR co-expression also reduces the adherence of CXCR4-expressing cells to various components of the extracellular matrix (ECM) and influences the partitioning of beta1 and alpha-v integrins to membrane lipid-rafts, affecting ECM-dependent signaling. uPAR interference in CXCR4 activity has been confirmed in cells from prostate carcinoma. Our results demonstrate that uPAR expression regulates the adhesive and migratory ability of CXCR4-expressing cells through a mechanism involving fMLP receptors and alpha-v integrins. 相似文献
868.
This review describes the properties of some rare eukaryotic chaperones that each assist in the folding of only one target
protein. In particular, we describe (1) the tubulin cofactors, (2) p47, which assists in the folding of collagen, (3) α-hemoglobin
stabilizing protein (AHSP), (4) the adenovirus L4-100 K protein, which is a chaperone of the major structural viral protein,
hexon, and (5) HYPK, the huntingtin-interacting protein. These various-sized proteins (102–1,190 amino acids long) are all
involved in the folding of oligomeric polypeptides but are otherwise functionally unique, as they each assist only one particular
client. This raises a question regarding the biosynthetic cost of the high-level production of such chaperones. As the clients
of faithful chaperones are all abundant proteins that are essential cellular or viral components, it is conceivable that this
necessary metabolic expenditure withstood evolutionary pressure to minimize biosynthetic costs. Nevertheless, the complexity
of the folding pathways in which these chaperones are involved results in error-prone processes. Several human disorders associated
with these chaperones are discussed. 相似文献
869.
Chen ZW 《Cellular and molecular life sciences : CMLS》2011,68(14):2409-2417
Accumulating evidence suggests that human γδ T cells act as non-classical T cells and contribute to both innate and adaptive
immune responses in infections. Vγ2 Vδ2 T (also termed Vγ9 Vδ2 T) cells exist only in primates, and in humans represent a
dominant circulating γδ T-cell subset. Primate Vγ2 Vδ2 T cells are the only γδ T cell subset capable of recognizing microbial
phosphoantigen. Since nonhuman primate Vγ2 Vδ2 T cells resemble their human counterparts, in-depth studies have been undertaken
in macaques to understand the biology and function of human Vγ2 Vδ2 T cells. This article reviews the recent progress for
immune biology of Vγ2 Vδ2 T cells in infections. 相似文献
870.
Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines
is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel
SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through
SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane
segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent
crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current
understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with
a new model for SecA-mediated protein translocation that unifies previous conflicting data. 相似文献