On November 13, 1997, the saber-toothed tiger logo was unveiled for the first time with the Predators insignia attached to it. On February 12, 1998, Head Coach Barry Trotz and Assistant Coach Paul Gardner unveiled the Predators' inaugural home and away jerseys at Cool Springs Galleria. During the inaugural season, the shoulder logo (an 'N' featuring the Bridgestone Arena spire) included the first year of the team's existence: '98.' In the 2005-06 season, the original shoulder patch was replaced by the skull logo originally worn on the Predators alternate jersey.
The jerseys - which feature prominent Gold striping, a script crest, felt block lettering and a redesigned Pred Head shoulder patch - pay homage to the Dixie Flyers, Nashville's first professional ice hockey team, which played from 1962 to 1971.
A throwback \"Nashville\" wordmark sits above the Pred Head and a vintage black and orange NHL shield replaces the modern silver and black emblem. On the shoulders, the Preds Star Pick patch has been replaced by the prehistoric skull Pred Head logo. Vintage Preds lettering and numbering adorns the jersey's back and nameplate as well.
Az alapgrafika kicsit módosult, akárcsak a játék nehézsége. Érdekesség, hogy új csapatként bekerült a Gyergyószentmiklósi Progym. A fejlesztők elmondták, hogy a Progymtól már a tavalyi évben is megkeresték őket, hogy szeretnének szerepelni a játékban, de megfelelő anyag hiányában akkor kimaradtak a patchből. Idén minden rendelkezésre állt, így nem volt akadálya annak, hogy bekerüljenek a játékba.
Átalakították a bajnokság rendszerét is, szétválasztották a MOL Ligát és az abban nem induló magyar csapatokat. Kivételt képez ez alól a már említett Progym, mely nyolcadik csapatként már idéntől a MOL Ligában indul, legalábbis a PC-s változatban. A tavaly még MOL ligásként szerepeltetett többi magyar csapat, így a Sapa Fehérvár AV19 is, választható opcióként átkerült a Custom csapatokhoz. A fejlesztői közösség elmondása szerint, ha idejük engedi és minden anyag a rendelkezésükre áll, akkor a közeljövőben megpróbálkoznak az EBEL patch elkészítésével is.
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TRIM proteins constitute a large, diverse and ancient protein family which play a key role in processes including cellular differentiation, autophagy, apoptosis, DNA repair, and tumour suppression. Mostly known and studied through the lens of their ubiquitination activity as E3 ligases, it has recently emerged that many of these proteins are involved in direct RNA binding through their NHL or PRY/SPRY domains. We summarise the current knowledge concerning the mechanism of RNA binding by TRIM proteins and its biological role. We discuss how RNA-binding relates to their previously described functions such as E3 ubiquitin ligase activity, and we will consider the potential role of enrichment in membrane-less organelles.
From a biochemical point of view, TRIM proteins constitute one of the largest subfamilies of ubiquitin E3 ligases found in the animal kingdom (Crawford et al., 2018) (Figure 1). Although first thought to be metazoan-specific, members of this family have now been identified in plants and fungi, highlighting its long evolutionary history (Sardiello et al., 2008; Marín, 2012; Crawford et al., 2018). The TRIM family is characterised by the presence of three distinct N-terminal domains: the RING domain, one or two B-boxes, and a coiled-coil region (RBCC), invariably ordered in this sequence from N- to C-terminus (Reymond et al., 2001) (Figure 2). To date, at least 77 TRIM proteins have been identified in humans, some of which lack components of the RBCC region but are evolutionarily closely related (Hatakeyama, 2017). In addition, 18 TRIM family members have been identified in Caenorhabditis elegans, seven in Drosophila melanogaster and more than 200 in zebrafish, underscoring the functional adaptability of this tripartite domain arrangement across species (Reymond et al., 2001; Sardiello et al., 2008; Langevin et al., 2019).
The most well-established biochemical function of TRIM proteins is the catalysis of the third step in the ubiquitination cascade, acting as RING E3 ligases to covalently modify protein substrates with ubiquitin (Ub) (Chu and Yang, 2010; Buetow and Huang, 2016) (Figure 3A, B). The RING domain mediates this reaction by binding the Ub-loaded E2 conjugating enzyme and positioning the Ub moiety in the correct orientation (Buetow and Huang, 2016) (Figure 3C). Upon association of the RING domain and the E2 Ub conjugate, a conserved cysteine in the E2 is poised for catalysis. The reaction typically results in the formation of an isopeptide bond between the carboxy-terminal glycine residue of Ub and a lysine residue on the substrate, although other residues can be involved (Buetow and Huang, 2016). In addition, TRIM proteins have been shown to become auto-ubiquitinated in a functionally relevant manner, such as in the case of TRIM5α and TRIM25 (Diaz-Griffero et al., 2006; Choudhury et al., 2017).
(A) The ubiquitination cascade involves an E1 activating enzyme that binds ATP and catalyses the formation of a thioester bond (represented by ) with ubiquitin (Ub). The E2 conjugating enzyme transfers Ub to its cysteine active site to form a second thioester linkage. In the presence of a substrate (S) and a RING-containing TRIM protein, the latter can act as an E3 ligase to modify residues such as lysine on the substrate. (B) Different types of Ub linkages result in a range of chain lengths and topologies, which can have different downstream effects [see Akutsu et al. (2016) for a comprehensive review]. (C) RING-containing E3s associate with the Ub-conjugated E2 to aid catalysis. Shown is the crystal structure of the RING domain of TRIM25 in complex with UbUBCH5A (E2) (Koliopoulos et al., 2016) (PDB:5FER).
With multiple ligation cycles, the target protein can become multi-mono-ubiquitinated and poly-ubiquitinated, resulting in chains of various topologies and lengths (Figure 3B) [see Akutsu et al. (2016) for a comprehensive review]. The diversity in the locations and types of ubiquitin linkages makes this post-translational modification highly versatile. Lysine 48 (K48) ubiquitination, for instance, normally targets proteins for degradation through the proteasome system. Sequence motifs present in a protein substrate that regulate its stability through ubiquitin-mediated degradation or ubiquitin-independent pathways are called degrons. These are short linear motifs that are important for substrate targeting but are not themselves ubiquitinated (Meszaros et al., 2017). Due to the lack of sufficient data it is difficult, however, to define a degron motif for TRIM family members at this point. In contrast to K48 linkages, ubiquitination through lysine 63 (K63) forms more linear ubiquitin chains with roles in DNA repair and endocytosis (Akutsu et al., 2016). Additionally, a relatively high number of TRIM members can add the Small Ubiquitin-like Modifier (SUMO) through interaction with the corresponding conjugating enzyme UBC9 (Chu and Yang, 2010). TRIM28, for instance, is able to modify IRF7 with SUMO, thereby inhibiting its activity (Liang et al., 2011). Additionally, TRIM25 can ligate the ubiquitin-like ISG15 protein to several substrates in response to viral infection (Martin-Vicente et al., 2017). Therefore, the TRIM family is able to catalyse a wide variety of modification and linkage types, consistent with its extensive involvement in many different biological pathways. Notably, some TRIM proteins like Drosophila BRAT do not contain a RING domain and it is unclear whether these can act as E3 ligases (Figure 2). However, in the case of TRIM16, co-immunoprecipitation studies showed that it can homo- and hetero-oligomerize with other TRIM members and have ubiquitination activity despite lacking a classical RING domain (Bell et al., 2012).
Several salient reviews on TRIM proteins have highlighted their role in immunity during viral infection (Nisole et al., 2005; Gack et al., 2007; Ozato et al., 2008; Sparrer and Gack, 2018; van Gent et al., 2018) and in disease processes (Hatakeyama, 2011; Tocchini and Ciosk, 2015; Hatakeyama, 2017; Watanabe and Hatakeyama, 2017; Crawford et al., 2018). For more focussed syntheses of TRIM protein function as ubiquitin E3 ligases, the reader is referred to overviews by Ikeda and Inoue (2012) and Ebner et al. (2017). In this review, we will focus on TRIM family members for which there exists clear evidence of RNA binding such as those containing the PRY/SPRY and NHL domains, and discuss potential functional and structural links between their ligase function and association with RNA.
Finally, TRIM56, which is often not included in discussions of NHL-TRIM proteins but is closely related and possesses NHL-like repeats (Liu et al., 2016), has been identified to be part of the human RNA interactome (Kwon et al., 2013). It is a key component of the Toll like receptor 3 (dsRNA sensing) pathway and inhibits the replication of influenza viruses, however this activity is dependent only on a 63 amino acid-long segment of the C-terminus, not on a fully formed NHL domain (Shen et al., 2012; Liu et al., 2016). However, in the case of bovine diarrhoea virus, the entire C-terminus as well as the E3 ubiquitin ligase activity were necessary to restrict viral RNA replication (Wang et al., 2011). A review by Garcia-Moreno et al. (2018) drew parallels between the RNA binding dependence of E3 ligase activity observed in TRIM25 by Choudhury et al. (2017) and the potential for a similar mechanism for TRIM56.
An allosteric effect of RNA-binding on ubiquitin E3 ligase activity would most likely be accomplished by facilitating interactions between the substrate which recognises the PRY/SPRY domain and the catalytic RING fi