Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

3D Structural View of Pathogen Recognition by Mammalian Lectin Receptors.

ABSTRACT: Humans and other mammals resist exogenous pathogens by recognizing them as non-self. How do they do this? The answer lies in the recognition by mammalian lectin receptors of glycans usually found on the surface of pathogens and whose chemical structure is species-specific. Some glycan components, such as galactofuranose, only occur in microbes, and is the principal means by which mammalian lectin receptors recognize non-self. Several lectins may function together as pattern recognition receptors to survey the infecting pathogen before the adaptive immune system is invoked. Most lectins have primary and secondary monosaccharide-binding sites which together determine the specificity of a receptor toward microbial glycans. There may also be a hydrophobic groove alongside the sugar binding sites that increases specificity. Another elaboration is through oligomerization of lectin domains with defined spacing and arrangement that creates high-affinity binding towards multiply-presented glycans on microbes. Microbe-specific polysaccharides may arise through unique sugar linkages. Specificity can come from mammalian receptors possessing a shallow binding site and binding only internal disaccharide units, as in the recognition of mannan by Dectin-2. The accumulation of 3D structural information on lectins receptors has allowed the recognition modes of microbe glycans to be classified into several groupings. This review is an introduction to our current knowledge on the mechanisms of pathogen recognition by representative mammalian lectin receptors.

SUBMITTER: Manabe N

PROVIDER: S-EPMC8185196 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Structural insight into the recognition of pathogen-derived phosphoglycolipids by C-type lectin receptor DCAR.

Project description:The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8-2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168-170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs.

| S-EPMC7186165 | biostudies-literature

A structural view of microRNA-target recognition.

Project description:It is well established that the correct identification of the messenger RNA targeted by a given microRNA (miRNA) is a difficult problem, and that available methods all suffer from low specificity. We hypothesize that the correct identification of the pairing should take into account the effect of the Argonaute protein (AGO), an essential catalyst of the recognition process. Therefore, we developed a strategy named MiREN for building and scoring three-dimensional models of the ternary complex formed by AGO, a miRNA and 22 nt of a target mRNA that putatively interacts with it. We show here that MiREN can be used to assess the likelihood that an RNA molecule is the target of a given miRNA and that this approach is more accurate than other existing methods, usually based on sequence or sequence-related features. Our results also suggest that AGO plays a relevant role in the selection of the miRNA targets. Our method can represent an additional step for refining predictions made by faster but less accurate classical methods for the identification of miRNA targets.

| S-EPMC4872079 | biostudies-literature

Structural basis for langerin recognition of diverse pathogen and mammalian glycans through a single binding site.

Project description:Langerin mediates the carbohydrate-dependent uptake of pathogens by Langerhans cells in the first step of antigen presentation to the adaptive immune system. Langerin binds to an unusually diverse number of endogenous and pathogenic cell surface carbohydrates, including mannose-containing O-specific polysaccharides derived from bacterial lipopolysaccharides identified here by probing a microarray of bacterial polysaccharides. Crystal structures of the carbohydrate-recognition domain from human langerin bound to a series of oligomannose compounds, the blood group B antigen, and a fragment of ?-glucan reveal binding to mannose, fucose, and glucose residues by Ca(2+) coordination of vicinal hydroxyl groups with similar stereochemistry. Oligomannose compounds bind through a single mannose residue, with no other mannose residues contacting the protein directly. There is no evidence for a second Ca(2+)-independent binding site. Likewise, a ?-glucan fragment, Glc?1-3Glc?1-3Glc, binds to langerin through the interaction of a single glucose residue with the Ca(2+) site. The fucose moiety of the blood group B trisaccharide Gal?1-3(Fuc?1-2)Gal also binds to the Ca(2+) site, and selective binding to this glycan compared to other fucose-containing oligosaccharides results from additional favorable interactions of the nonreducing terminal galactose, as well as of the fucose residue. Surprisingly, the equatorial 3-OH group and the axial 4-OH group of the galactose residue in 6SO(4)-Gal?1-4GlcNAc also coordinate Ca(2+), a heretofore unobserved mode of galactose binding in a C-type carbohydrate-recognition domain bearing the Glu-Pro-Asn signature motif characteristic of mannose binding sites. Salt bridges between the sulfate group and two lysine residues appear to compensate for the nonoptimal binding of galactose at this site.

| S-EPMC3065333 | biostudies-literature

Recognition of Tumor Nidogen-1 by Neutrophil C-Type Lectin Receptors.

Project description:Neutrophil-mediated cytotoxicity toward tumor cells requires cell contact and is mediated by hydrogen peroxide. We have recently shown that Cathepsin G expressed on the neutrophil surface interacts with tumor RAGE, and this interaction facilitates neutrophil cytotoxicity. Interruption of the Cathepsin G-RAGE interaction led to 50-80% reduction in cytotoxicity, suggesting that additional interactions are also involved. Here we show that blocking antibodies to the C-type lectin receptors (CLRs) Clec4e and Dectin-1, but not those to NKG2D, attenuated murine neutrophil cytotoxicity towards murine tumor cells, suggesting a contributing role for these CLRs in neutrophil recognition of tumor cells. We further observed that the CLRs interact with tumor Nidogen-1 and Hspg2, two sulfated glycoproteins of the basement membrane. Both Nidogen-1 and Hspg2 were found to be expressed on the tumor cell surface. The knockdown of Nidogen-1, but not that of Hspg2, led to reduced susceptibility of the tumor cells to neutrophil cytotoxicity. Altogether, this study suggests a role for CLR-Nidogen-1 interaction in the recognition of tumor cells by neutrophils, and this interaction facilitates neutrophil-mediated killing of the tumor cells.

| S-EPMC9030733 | biostudies-literature

The origin recognition complex: a biochemical and structural view.

Project description:The origin recognition complex (ORC) was first discovered in the baker's yeast in 1992. Identification of ORC opened up a path for subsequent molecular level investigations on how eukaryotic cells initiate and control genome duplication each cell cycle. Twenty years after the first biochemical isolation, ORC is now taking on a three-dimensional shape, although a very blurry shape at the moment, thanks to the recent electron microscopy and image reconstruction efforts. In this chapter, we outline the current biochemical knowledge about ORC from several eukaryotic systems, with emphasis on the most recent structural and biochemical studies. Despite many species-specific properties, an emerging consensus is that ORC is an ATP-dependent machine that recruits other key proteins to form pre-replicative complexes (pre-RCs) at many origins of DNA replication, enabling the subsequent initiation of DNA replication in S phase.

| S-EPMC3779782 | biostudies-literature

Ligands of Adrenergic Receptors: A Structural Point of View.

Project description:Adrenergic receptors are G protein-coupled receptors for epinephrine and norepinephrine. They are targets of many drugs for various conditions, including treatment of hypertension, hypotension, and asthma. Adrenergic receptors are intensively studied in structural biology, displayed for binding poses of different types of ligands. Here, we summarized molecular mechanisms of ligand recognition and receptor activation exhibited by structure. We also reviewed recent advances in structure-based ligand discovery against adrenergic receptors.

| S-EPMC8301793 | biostudies-literature

From structure to function - Ligand recognition by myeloid C-type lectin receptors.

Project description:The relevance of protein-glycan interactions in immunity has long been underestimated. Yet, the immune system possesses numerous classes of glycan-binding proteins, so-called lectins. Of specific interest is the group of myeloid C-type lectin receptors (CLRs) as they are mainly expressed by myeloid cells and play an important role in the initiation of an immune response. Myeloid CLRs represent a major group amongst pattern recognition receptors (PRRs), placing them at the center of the rapidly growing field of glycoimmunology. CLRs have evolved to encompass a wide range of structures and functions and to recognize a large number of glycans and many other ligands from different classes of biopolymers. This review aims at providing the reader with an overview of myeloid CLRs and selected ligands, while highlighting recent insights into CLR-ligand interactions. Subsequently, methodological approaches in CLR-ligand research will be presented. Finally, this review will discuss how CLR-ligand interactions culminate in immunological functions, how glycan mimicry favors immune escape by pathogens, and in which way immune responses can be affected by CLR-ligand interactions in the long term.

| S-EPMC9630629 | biostudies-literature

Human adenovirus binding to host cell receptors: a structural view.

Project description:Human Adenoviruses (HAdVs) are a family of clinically and therapeutically relevant viruses. A precise understanding of their host cell attachment and entry mechanisms can be applied in inhibitor design and the construction of targeted gene delivery vectors. In this article, structural data on adenovirus attachment and entry are reviewed. HAdVs engage two types of receptors: first, an attachment receptor that is bound by the fibre knob protein protruding from the icosahedral capsid, and next, an integrin entry receptor bound by the pentameric penton base at the capsid vertices. Adenoviruses use remarkably diverse attachment receptors, five of which have been studied structurally in the context of HAdV binding: Coxsackie and Adenovirus Receptor, CD46, the glycans GD1a and polysialic acid, and desmoglein-2. Together with the integrin entry receptors, they display both symmetrical and asymmetrical modes of binding to the virus as demonstrated by the structural analyses reviewed here. The diversity of HAdV receptors contributes to the broad tropism of these viruses, and structural studies are thus an important source of information on HAdV-host cell interactions. The imbalance in structural data between the more and less extensively studied receptors remains to be addressed by future research.

| S-EPMC7248032 | biostudies-literature

Structural basis for multiple sugar recognition of Jacalin-related human ZG16p lectin.

Project description:ZG16p is a soluble mammalian lectin, the first to be described with a Jacalin-related β-prism-fold. ZG16p has been reported to bind both to glycosaminoglycans and mannose. To determine the structural basis of the multiple sugar-binding properties, we conducted glycan microarray analyses of human ZG16p. We observed that ZG16p preferentially binds to α-mannose-terminating short glycans such as Ser/Thr-linked O-mannose, but not to high mannose-type N-glycans. Among sulfated glycosaminoglycan oligomers examined, chondroitin sulfate B and heparin oligosaccharides showed significant binding. Crystallographic studies of human ZG16p lectin in the presence of selected ligands revealed the mechanism of multiple sugar recognition. Manα1-3Man and Glcβ1-3Glc bound in different orientations: the nonreducing end of the former and the reducing end of the latter fitted in the canonical shallow mannose binding pocket. Solution NMR analysis using (15)N-labeled ZG16p defined the heparin-binding region, which is on an adjacent flat surface of the protein. On-array competitive binding assays suggest that it is possible for ZG16p to bind simultaneously to both types of ligands. Recognition of a broad spectrum of ligands by ZG16p may account for the multiple functions of this lectin in the formation of zymogen granules via glycosaminoglycan binding, and in the recognition of pathogens in the digestive system through α-mannose-related recognition.

| S-EPMC4059138 | biostudies-literature

Structural basis for molecular recognition at serotonin receptors.

Project description:Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs.

| S-EPMC3644373 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data