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The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface.

ABSTRACT: Many capsid proteins have peptides that influence their assembly. In hepatitis B virus capsid protein, the peptide STLPETTVV, linking the shell-forming 'core' domain and the nucleic acid-binding 'protamine' domain, has such a role. We have studied its morphogenic properties by permuting its sequence, substituting it with an extraneous peptide, deleting it to directly fuse the core and protamine domains and assembling core domain dimers with added linker peptides. The peptide was found to be necessary for the assembly of protamine domain-containing capsids, although its size-determining effect tolerates some modifications. Although largely invisible in a capsid crystal structure, we could visualize linker peptides by cryo-EM difference imaging: they emerge on the inner surface and extend from the capsid protein dimer interface towards the adjacent symmetry axis. A closely sequence-similar peptide in cellobiose dehydrogenase, which has an extended conformation, offers a plausible prototype. We propose that linker peptides are attached to the capsid inner surface as hinged struts, forming a mobile array, an arrangement with implications for morphogenesis and the management of encapsidated nucleic acid.

SUBMITTER: Watts NR

PROVIDER: S-EPMC125892 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature

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The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface.

Watts Norman R NR Conway James F JF Cheng Naiqian N Stahl Stephen J SJ Belnap David M DM Steven Alasdair C AC Wingfield Paul T PT

The EMBO journal 20020301 5

Many capsid proteins have peptides that influence their assembly. In hepatitis B virus capsid protein, the peptide STLPETTVV, linking the shell-forming 'core' domain and the nucleic acid-binding 'protamine' domain, has such a role. We have studied its morphogenic properties by permuting its sequence, substituting it with an extraneous peptide, deleting it to directly fuse the core and protamine domains and assembling core domain dimers with added linker peptides. The peptide was found to be nece ...[more]

PMID: 11867516

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Project description:Identification of immunogenic targets against hepatitis B virus (HBV)-encoded proteins will provide crucial advances in developing potential antibody therapies. In this study, 63 treatment-naïve patients with chronic HBV infection and 46 patients who achieved hepatitis B surface antigen loss (sAg loss) following antiviral treatment were recruited. Moreover, six patients who transitioned from the hepatitis B e antigen-positive chronic infection phase (eAg+CInf) to the hepatitis phase (eAg+CHep) were enrolled from real-life clinical practice. Additionally, telbivudine-treated eAg+CHep patients and relapsers or responders from an off-treatment cohort were longitudinally studied. The frequencies and function of B cells were assessed by flow cytometry. We devised a peptide array composed of 15-mer overlapping peptides of HBV-encoded surface (S), core (C), and polymerase (P) proteins and performed a screening on B-cell linear epitopes with sera. Naïve B cells and plasmablasts were increased, whereas total memory, activated memory (AM), and atypical memory (AtM) B cells were reduced in sAg- patients compared with sAg+ patients. Importantly, longitudinal observations found that AtM B cells were associated with successful treatment withdrawal. Interestingly, we identified six S-specific dominant epitopes (S33, S34, S45, S76, S78, and S89) and one C-specific dominant epitope (C37) that reacted with the majority of sera from sAg- patients. Of note, more B-cell linear epitopes were detected in CHep patients with alanine aminotransferase (ALT) flares than in nonflare CInf patients, and five B-cell linear epitopes (S4, S5, S10, S11, and S68) were overwhelmingly recognized by ALT flare patients. The recognition rates of epitopes on C and P proteins were significantly increased in CHep patients relative to CInf patients. Strikingly, a statistically significant elevation in the number of positive epitopes was observed when ALT nonflare patients shifted into the flare phase. Moreover, S76 identified at baseline was confirmed to be associated with a complete response after 48 weeks of telbivudine therapy. Taken together, we identified several functional cure-related B-cell linear epitopes of chronic HBV infection, and these epitopes may serve as vaccine candidates to elicit neutralizing antibodies to treat HBV infection.

Project description:Background and objectivesThis study was conducted by the International Consortium for Blood Safety (ICBS) to identify high-quality test kits for detection of hepatitis B virus (HBV) surface antigen (HBsAg) for the benefit of developing countries.Materials and methodsThe 70 HBsAg test kits from around the world were evaluated comparatively for their clinical sensitivity, analytical sensitivity, sensitivity to HBV genotypes and HBsAg subtypes, and specificity using 394 (146 clinical, 48 analytical and 200 negative) ICBS Master Panel members of diverse geographical origin comprising the major HBV genotypes A-F and the HBsAg subtypes adw2,4, adr and ayw1-4.ResultsSeventeen HBsAg enzyme immunoassay (EIA) kits had high analytical sensitivity <0.13 IU/ml, showed 100% diagnostic sensitivity, and were even sensitive for the various HBV variants tested. An additional six test kits had high sensitivity (<0.13 IU/ml) but missed HBsAg mutants and/or showed reduced sensitivity to certain HBV genotypes. Twenty HBsAg EIA kits were in the sensitivity range of 0.13-1 IU/ml. The other eight EIAs and the 19 rapid assays had analytical sensitivities of 1 to >4 IU/ml. These assays were falsely negative for 1-4 clinical samples and 17 of these test kits showed genotype dependent sensitivity reduction. Analytical sensitivities for HBsAg of >1 IU/ml significantly reduce the length of the HBsAg positive period which renders them less reliable for detecting HBsAg in asymptomatic HBV infections. Reduced sensitivity for HBsAg with genetic diversity of HBV occurred with genotypes/subtypes D/ayw3, E/ayw4, F/adw4 and by S gene mutants. Specificity of the HBsAg assays was >or=99.5% in 57 test kits and 96.4-99.0% in the remaining test kits.ConclusionDiagnostic efficacy of the evaluated HBsAg test kits differed substantially. Laboratories should therefore be aware of the analytical sensitivity for HBsAg and check for the relevant HBV variants circulating in the relevant population.

Project description:Although many plants are dispersed by wind and seeds can travel long distances across unsuitable matrix areas, a large proportion relies on co-evolved zoochorous seed dispersal to connect populations in isolated habitat islands. Particularly in agricultural landscapes, where remaining habitat patches are often very small and highly isolated, mobile linkers as zoochorous seed dispersers are critical for the population dynamics of numerous plant species. However, knowledge about the quali- or quantification of such mobile link processes, especially in agricultural landscapes, is still limited. In a controlled feeding experiment, we recorded the seed intake and germination success after complete digestion by the European brown hare (Lepus europaeus) and explored its mobile link potential as an endozoochoric seed disperser. Utilizing a suite of common, rare, and potentially invasive plant species, we disentangled the effects of seed morphological traits on germination success while controlling for phylogenetic relatedness. Further, we measured the landscape connectivity via hares in two contrasting agricultural landscapes (simple: few natural and semi-natural structures, large fields; complex: high amount of natural and semi-natural structures, small fields) using GPS-based movement data. With 34,710 seeds of 44 plant species fed, one of 200 seeds (0.51%) with seedlings of 33 species germinated from feces. Germination after complete digestion was positively related to denser seeds with comparatively small surface area and a relatively slender and elongated shape, suggesting that, for hares, the most critical seed characteristics for successful endozoochorous seed dispersal minimize exposure of the seed to the stomach and the associated digestive system. Furthermore, we could show that a hare's retention time is long enough to interconnect different habitats, especially grasslands and fields. Thus, besides other seed dispersal mechanisms, this most likely allows hares to act as effective mobile linkers contributing to ecosystem stability in times of agricultural intensification, not only in complex but also in simple landscapes.

Dataset Information

The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface.

Publications

The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface.

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