The contracted tail of myophage vb_EcoM_CBA120 (CBA120)
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ABSTRACT:
SUBMITTER: Sergey Nazarov
PROVIDER: EMPIAR-10505 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:Remarkable progress has been made during the past ten years in elucidating the structure of the bacteriophage T4 tail by a combination of three-dimensional image reconstruction from electron micrographs and X-ray crystallography of the components. Partial and complete structures of nine out of twenty tail structural proteins have been determined by X-ray crystallography and have been fitted into the 3D-reconstituted structure of the "extended" tail. The 3D structure of the "contracted" tail was also determined and interpreted in terms of component proteins. Given the pseudo-atomic tail structures both before and after contraction, it is now possible to understand the gross conformational change of the baseplate in terms of the change in the relative positions of the subunit proteins. These studies have explained how the conformational change of the baseplate and contraction of the tail are related to the tail's host cell recognition and membrane penetration function. On the other hand, the baseplate assembly process has been recently reexamined in detail in a precise system involving recombinant proteins (unlike the earlier studies with phage mutants). These experiments showed that the sequential association of the subunits of the baseplate wedge is based on the induced-fit upon association of each subunit. It was also found that, upon association of gp53 (gene product 53), the penultimate subunit of the wedge, six of the wedge intermediates spontaneously associate to form a baseplate-like structure in the absence of the central hub. Structure determination of the rest of the subunits and intermediate complexes and the assembly of the hub still require further study.
| S-EPMC3004832 | biostudies-literature
Project description:Bacteriophages are viruses infecting bacteria. The vast majority of them bear a tail, allowing host recognition, cell wall perforation, and DNA injection into the host cytoplasm. Using electron cryo-microscopy (cryo-EM) and single particle analysis, we determined the organization of the tail proximal extremity of siphophage T5 that possesses a long flexible tail and solved the structure of its tail terminator protein p142 (TrP142). It allowed us to confirm the common evolutionary origin between T5 TrPp142 and other known or putative TrPs from siphophages, myophages, and bacterial tail-like machines, despite very poor sequence conservation. By also determining the structure of the T5 tail proximal extremity after interaction with T5 bacterial receptor FhuA, we showed that no conformational changes occur in TrPp142 and confirmed that the infection signal transduction is not carried by the tube itself. We also investigated the location of T5 Neck1 or tail completion protein p143 (TCPp143) and showed, thanks to a combination of cryo-EM and structure prediction using Alphafold2, that it is not located at the capsid-to-tail interface as suggested by its position in the genome, but instead, very unexpectedly, on the side of T5 tail tip, and that it appears to be monomeric. Based on structure comparison with other putative TCPs predicted structures, this feature could not be shared by other TCPs and questions the affiliation of p143 to this family of protein.IMPORTANCEBacteriophages, viruses infecting bacteria, are the most abundant living entities on Earth. They are present in all ecosystems where bacteria develop and are instrumental in the regulation, diversity, evolution, and pathogeny of microbial populations. Moreover, with the increasing number of pathogenic strains resistant to antibiotics, virulent phages are considered a serious alternative or complement to classical treatments. 96% of all phages present a tail that allows host recognition and safe channeling of the DNA to the host cytoplasm. We present the atomic model of the proximal extremity of the siphophage T5 tail, confirming structural similarities with other phages. This structure, combined with results previously published and further explored, also allowed a review and a discussion on the role and localization of a mysterious tail protein, the tail completion protein, which is known to be present in the phage tails, but that was never identified in a phage structure.
| S-EPMC11784142 | biostudies-literature
Project description:BackgroundAssuming that tail length is associated with the prevalence of tail biting, attempts are being made to shorten tails by genetic selection in order to avoid the painful procedure of docking. However, undesirable side effects such as kinky tails and inflammatory changes may occur. The aim of the present study was to clinically quantify in a population with known segregation of tail length, i) its variability, ii) possible associations with kinked tails and iii) possible associations of tail length and kinks with inflammation of the tail using 348 piglets at day 3 (undocked) and 39 (docked tails) of life.ResultsThe relative tail length (tail tip to tail base/tail tip to ear base × 100) varied between 20.3 and 31.3%. A reduced tail length was associated with kinked tails. Piglets with the shortest tails had 28% kinked tails, 5.6 times more than the piglets with the longest tails. The tails showed high prevalence of inflammation both on day 3 and on the docked tails on day 39. Overall, these were not associated with tail length or kinked tails. Only necrosis of the tail was significantly more frequent in the kinked tails than in the normal tails. Sow line, sow ID and boar ID significantly affected relative tail length, which may suggest a genetic cause.ConclusionBased on the phenotypic variation found in the present study, it seems possible to influence tail length through breeding. It remains to be seen whether the available potential is sufficient to actually reduce tail biting. At the same time, a higher incidence of kinked tails and necrosis is to be expected.
| S-EPMC11863879 | biostudies-literature
Project description:Siphophages have a long, flexible, and noncontractile tail that connects to the capsid through a neck. The phage tail is essential for host cell recognition and virus-host cell interactions; moreover, it serves as a channel for genome delivery during infection. However, the in situ high-resolution structure of the neck-tail complex of siphophages remains unknown. Here, we present the structure of the siphophage lambda "wild type," the most widely used, laboratory-adapted fiberless mutant. The neck-tail complex comprises a channel formed by stacked 12-fold and hexameric rings and a 3-fold symmetrical tip. The interactions among DNA and a total of 246 tail protein molecules forming the tail and neck have been characterized. Structural comparisons of the tail tips, the most diversified region across the lambda and other long-tailed phages or tail-like machines, suggest that their tail tip contains conserved domains, which facilitate tail assembly, receptor binding, cell adsorption, and DNA retaining/releasing. These domains are distributed in different tail tip proteins in different phages or tail-like machines. The side tail fibers are not required for the phage particle to orient itself vertically to the surface of the host cell during attachment.
| S-EPMC10721106 | biostudies-literature
Project description:Immune-checkpoint inhibitors have deeply changed the therapeutic landscape of advanced non-small cell lung cancer without actionable genomic alterations. Immune-checkpoint inhibitors have become standard front-line therapy, especially among patients with tumours expressing high levels of programmed death ligand-1; yet, many patients do not respond to therapy. This has led to the adoption of front-line combination therapies, administering programmed death-1 inhibitors concomitantly either with other checkpoint inhibitors, chemotherapy or both. Today's approved standard of care includes options with chemoimmunotherapy or dual checkpoint blockade, but each combination has only been compared to chemotherapy alone and no head-to-head trials exist. In cross-trial comparisons, combinations trials appear to show numerically superior responses to single-agent checkpoint inhibitors but the question is whether they ultimately offer a survival advantage. In this manuscript, we summarize and analyse all currently available front-line immune-checkpoint inhibitor trials in non-small cell lung cancer, whether as monotherapy or in combination with chemotherapy, second immunotherapy agents or both. Should standards of care change given the current data? While we ponder this question, we illustrate current data and conclude that the answer lies in tracking the tail of the survival curves.
| S-EPMC7473618 | biostudies-literature
Project description:Tail biting is both an important economic and a welfare problem. The primary preventive measure, almost on a routine basis throughout Europe, remains tail docking following a risk analysis. This study aimed to get insight on the perceptions of Greek pig farmers towards tail docking, intervention measures, and risk factors of tail biting, as well as opinions on pig welfare themes. Eighty-two farmers answered a questionnaire provided online and in printed form. In the case of a tail-biting outbreak, the most important intervention measure is the removal of the bitten pig (victim), while feed quality, air movements, and stocking density were ranked as the highest risk factors (p ≤ 0.05). Chains are the most common type of enrichment by 67% followed by plastic objects by 29.5%. Almost half of the farmers reported having no tail-biting problem on their farm, while 64.4% of the respondents have already tried at least once to raise pigs with intact tails. To reduce routine tail docking, it is essential to apply specific farm-oriented solutions effectively. To succeed in this aim, it is important to consider farmers' concerns and practices. This study is the first step in that direction.
| S-EPMC9952019 | biostudies-literature
Project description:Phage G is recognized as having a remarkably large genome and capsid size among isolated, propagated phages. Negative stain electron microscopy of the host-phage G interaction reveals tail sheaths that are contracted towards the distal tip and decoupled from the head-neck region. This is different from the typical myophage tail contraction, where the sheath contracts upward, while being linked to the head-neck region. Our cryo-EM structures of the non-contracted and contracted tail sheath show that: (1) The protein fold of the sheath protein is very similar to its counterpart in smaller, contractile phages such as T4 and phi812; (2) Phage G's sheath structure in the non-contracted and contracted states are similar to phage T4's sheath structure. Similarity to other myophages is confirmed by a comparison-based study of the tail sheath's helical symmetry, the sheath protein's evolutionary timetree, and the organization of genes involved in tail morphogenesis. Atypical phase G tail contraction could be due to a missing anchor point at the upper end of the tail sheath that allows the decoupling of the sheath from the head-neck region. Explaining the atypical tail contraction requires further investigation of the phage G sheath anchor points.
| S-EPMC8570332 | biostudies-literature
Project description:Tail posture (i.e., hanging or curled) has been suggested to be an indicator of tail biting, and hanging tails predisposed to damage. The aim of this study was to investigate if tail posture was feasible as a tail damage indicator in a commercial setting. The study was carried out on one batch of 459 undocked finishing pigs (30⁻120 kg in weight). Weekly scoring of tail posture was combined with the scoring of tail lesions. Tail posture was observed at feeding to facilitate the usage of the method in commercial settings. A curly tail was observed in 94% of the observations. Pigs with tails scored with "wound" were 4.15 (p < 0.0001) times more likely to have hanging tails, and pigs scored with "inflamed wounds" were 14.24 (p < 0.0001) times more likely to have hanging tails, compared to pigs with nondamaged tails. Tail posture correctly classified tails with "wound" or "inflamed wound" 67.5% of the time, with 55.2% sensitivity and 79.7% specificity, respectively. The method of observing the tail position at feeding seems useful as a complement to normal inspection for detecting tail biting before tail wounds are visible to the caretaker.
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Project description:Different sheep breeds show distinct phenotypic plasticity in fat deposition in the tails. The genetic background underlying fat deposition in the tail of sheep is complex, multifactorial, and may involve allele-specific expression (ASE) mechanism to modulate allelic expression. ASE is a common phenomenon in mammals and refers to allelic imbalanced expression modified by cis-regulatory genetic variants that can be observed at heterozygous loci. Therefore, regulatory processes behind the fat-tail formation in sheep may be to some extent explained by cis- regulatory variants, through ASE mechanism, which was investigated in the present study. An RNA-Seq-based variant calling was applied to perform genome-wide survey of ASE genes using 45 samples from seven independent studies comparing the transcriptome of fat-tail tissue between fat- and thin-tailed sheep breeds. Using a rigorous computational pipeline, 115 differential ASE genes were identified, which were narrowed down to four genes (LPL, SOD3, TCP1 and LRPAP1) for being detected in at least two studies. Functional analysis revealed that the ASE genes were mainly involved in fat metabolism. Of these, LPL was of greater importance, as 1) observed in five studies, 2) reported as ASE gene in the previous studies and 3) with a known role in fat deposition. Our findings implied that complex physiological traits, like fat-tail formation, can be better explained by considering various genetic mechanisms, which can be more finely mapped through ASE analyses. The insights gained in this study indicate that biallelic expression may not be a common mechanism in sheep fat-tail development. Hence, allelic imbalance of the fat deposition-related genes can be considered a novel layer of information for future research on genetic improvement and increased efficiency in sheep breeding programs.
| S-EPMC11676558 | biostudies-literature
Project description:Tail docking of neonatal pigs is widely used as a measure to reduce the incidence of tail biting, a complex management problem in the pig industry. Concerns exist over the long-term consequences of tail docking for possible tail stump pain sensitivity due to the development of traumatic neuromas in injured peripheral nerves. Tail stumps were obtained post mortem from four female pigs at each of 1, 4, 8 and 16 weeks following tail amputation (approximately two-thirds removed) by a gas-heated docking iron on post natal day 3. Tissues were processed routinely for histopathological examination. Non-neural inflammatory and reparative epidermal and dermal changes associated with tissue thickening and healing were observed 1 to 4 months after docking. Mild neutrophilic inflammation was present in some cases, although this and other degenerative and non-neural reparative changes are not likely to have caused pain. Traumatic neuroma and neuromatous tissue development was not observed 1 week after tail docking, but was evident 1 month after tail docking. Over time there was marked nerve sheath and axonal proliferation leading to the formation of neuromata, which were either localized and circumscribed or comprised of multiple axons dispersed within granulation tissue. Four months after tail resection, neuroma formation was still incomplete, with possible implications for sensitivity of the tail stump.
| S-EPMC4940206 | biostudies-literature