DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.

Detection of viral nucleic acids is central to antiviral immunity. Recently, DAI/ZBP1 (DNA-dependent activator of IRFs/Z-DNA binding protein 1) was identified as a cytoplasmic DNA sensor and shown to activate the interferon regulatory factor (IRF) and nuclear factor-kappa B (NF-kappaB) transcription factors, leading to type-I interferon production. DAI-induced IRF activation depends on TANK-binding kinase 1 (TBK1), whereas signalling pathways and molecular components involved in NF-kappaB activation remain elusive. Here, we report the identification of two receptor-interacting protein (RIP) homotypic interaction motifs (RHIMs) in the DAI protein sequence, and show that these domains relay DAI-induced NF-kappaB signals through the recruitment of the RHIM-containing kinases RIP1 and RIP3. We show that knockdown of not only RIP1, but also RIP3 affects DAI-induced NF-kappaB activation. Importantly, RIP recruitment to DAI is inhibited by the RHIM-containing murine cytomegalovirus (MCMV) protein M45. These findings delineate the DAI signalling pathway to NF-kappaB and suggest a possible new immune modulation strategy of the MCMV.

Homeodomain binding motifs modulate the probability of odorant receptor gene choice in transgenic mice.

Odorant receptor (OR) genes constitute with 1200 members the largest gene family in the mouse genome. A mature olfactory sensory neuron (OSN) is thought to express just one OR gene, and from one allele. The cell bodies of OSNs that express a given OR gene display a mosaic pattern within a particular region of the main olfactory epithelium. The mechanisms and cis-acting DNA elements that regulate the expression of one OR gene per OSN - OR gene choice - remain poorly understood. Here, we describe a reporter assay to identify minimal promoters for OR genes in transgenic mice, which are produced by the conventional method of pronuclear injection of DNA. The promoter transgenes are devoid of an OR coding sequence, and instead drive expression of the axonal marker tau-β-galactosidase. For four mouse OR genes (M71, M72, MOR23, and P3) and one human OR gene (hM72), a mosaic, OSN-specific pattern of reporter expression can be obtained in transgenic mice with contiguous DNA segments of only ~300 bp that are centered around the transcription start site (TSS). The ~150bp region upstream of the TSS contains three conserved sequence motifs, including homeodomain (HD) binding sites. Such HD binding sites are also present in the H and P elements, DNA sequences that are known to strongly influence OR gene expression. When a 19mer encompassing a HD binding site from the P element is multimerized nine times and added upstream of a MOR23 minigene that contains the MOR23 coding region, we observe a dramatic increase in the number of transgene-expressing founders and lines and in the number of labeled OSNs. By contrast, a nine times multimerized 19mer with a mutant HD binding site does not have these effects. We hypothesize that HD binding sites in the H and P elements and in OR promoters modulate the probability of OR gene choice.

Defining and searching for structural motifs using DeepView/Swiss-PdbViewer.

BACKGROUND: Today, recognition and classification of sequence motifs and protein folds is a mature field, thanks to the availability of numerous comprehensive and easy to use software packages and web-based services. Recognition of structural motifs, by comparison, is less well developed and much less frequently used, possibly due to a lack of easily accessible and easy to use software. RESULTS: In this paper, we describe an extension of DeepView/Swiss-PdbViewer through which structural motifs may be defined and searched for in large protein structure databases, and we show that common structural motifs involved in stabilizing protein folds are present in evolutionarily and structurally unrelated proteins, also in deeply buried locations which are not obviously related to protein function. CONCLUSIONS: The possibility to define custom motifs and search for their occurrence in other proteins permits the identification of recurrent arrangements of residues that could have structural implications. The possibility to do so without having to maintain a complex software/hardware installation on site brings this technology to experts and non-experts alike.

[Voyage en Italie : 1825-1830]. , [Enchevêtrement de motifs divers et décors d'arabesques] Au Musée de Florence : [deux motifs sculptés] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 159

[Voyage en Italie : 1825-1830]. , [Bas-reliefs] À Otricoli ; au Musée de Florence : [trois motifs sculptés] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 156

[Voyage en Italie : 1825-1830]. , [Bas-reliefs] Au Musée : [deux motifs sculptés] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 158

[Voyage en Italie : 1824-1830]. , Musée des Études : [seize motifs représentant des monuments, d'après des peintures ou des fresques antiques] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 287

[Voyage en Italie : 1824-1830]. , Musée des Etudes, Bronzes [détails d'ornements, lampe à huile] : [neuf motifs] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 257

[Voyage en Italie : 1824-1830]. , Musée des Etudes, Etrusques : [quatorze motifs : vases et divers détails] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 269

[Voyage en Italie : 1824-1830]. , Musée des Etudes, Etrusques : [treize motifs : vases et divers détails] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 270

[Voyage en Italie : 1824-1830]. , Musée des Etudes, Etrusques : [cinq motifs : trois vases et divers détails] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 271

[Voyage en Italie : 1824-1830]. , Musée des Etudes, Etrusques : [dix motifs : six vases et détails] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 272

[Voyage en Italie : 1824-1830]. , Musée des Etudes : [trois motifs : table, bandeaux historiés] : [dessin] / h. L. [Henri Labrouste]

Référence bibliographique : Weigert, 264

The number of Toll-like receptor 9-agonist motifs in the adenovirus genome correlates with induction of dendritic cell maturation by adenovirus immune complexes.

Adenovirus serotype 5 (Ad5) vectors and specific neutralizing antibodies (NAbs) generate immune complexes (ICs) which are potent inducers of dendritic cell (DC) maturation. Here we show that ICs generated with rare Ad vector serotypes, such as Ad26 and Ad35, which are lead candidates in HIV vaccine development, are poor inducers of DC maturation and that their potency in inducing DC maturation strongly correlated with the number of Toll-like receptor 9 (TLR9)-agonist motifs present in the Ad vector's genome. In addition, we showed that antihexon but not antifiber antibodies are responsible for the induction of Ad IC-mediated DC maturation.