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Terahertz vibrations are sensitive reporters of the structure and interactions of proteins. Ligand binding alters the nature and distribution of these collective vibrations. The ligand-induced changes in the terahertz protein vibrations contribute to the binding entropy and to the overall thermodynamic stability of the resultant protein-ligand complexes. Here, we have examined the response of the low-frequency (below 6 terahertz) collective vibrations of the calcium-loaded calmodulin (CaM) to binding to five different ligands, both in the presence and absence of water, using normal-mode analysis and molecular dynamics simulations. A comparison of the vibrational spectra of hydrated and dry systems reveals that protein-solvent interactions stiffen the terahertz protein vibrations and that these solvent-coupled collective vibrations contribute significantly to the hydration-sensitive variation in the vibrational entropy of CaM. In the absence of water, the low-frequency vibrations of CaM are stiffened by ligand binding. On the contrary, the number and the cumulative vibrational entropy of low-frequency vibrational modes (ω < 200 cm-1) of the hydrated CaM are increased noticeably after binding to the peptides, indicating binding-induced softening of collective vibrations of the protein. Although the calculated and experimental binding affinities of the chosen complexes correlated reasonably well, no systematic correlation was observed between the protein vibrational entropy and the binding affinity. The results underscored the importance of the interplay of protein-ligand and solvent interactions in modulating the low-frequency vibrations of proteins.

UNASSIGNED: Calmodulinopathy is an emerging group of primary electrical disease with various, severe, and early onset phenotype. Sudden cardiac arrest (SCA)/death can be the first symptom and current medical management seems insufficient to prevent recurrences. Implantable cardioverter-defibrillator (ICD) in the young is challenging and can be harmful.
UNASSIGNED: We report the management of two very young boys (aged 3.5 and 5.5 years old) who survived an SCA due to calmodulin mutation responsible of a catecholaminergic polymorphic ventricular tachycardia phenotype. In both case, SCA had an adrenergic trigger. Despite SCA, ICD implantation was denied by the parents. After thorough discussion with the family, the patients were managed with solely betablocker treatment and loop recorder implantation. At last follow-up of 30 and 23 months, respectively, there were no recurrence of any cardiac event.
UNASSIGNED: The benefits of ICD implantation at a very young age must be weighed against the risk complication. In the youngest, whom recreative activities are under constant supervision, the decision, jointly made with the parents, could be to postpone ICD.

UNASSIGNED: Calmodulin (CaM) is a multifunctional intermediate messenger protein that plays important role in cell motility, proliferation, and apoptosis. Therefore, it is thought to be involved in various ways in the apoptotic processes which are implicated in the pathogenesis of lichen planus.
UNASSIGNED: The aim of this study was to evaluate the immunohistochemical expression of CaM in lichen planus lesions in comparison to normal control skin to throw light on its possible role in disease pathogenesis.
UNASSIGNED: This case-control study was conducted on 50 patients with lichen planus, in addition to 20 age- and sex-matched healthy individuals. Skin biopsy specimens were taken from lesional skin of lichen planus patients as well as normal skin of controls. All were examined for immunohistochemical expression of CaM antibody.
UNASSIGNED: There was statistically significant increase of the immunohistochemical expression of CaM in lesional skin of lichen planus patients compared with normal skin of controls (Chi-square test, P < 0.001). No significant correlation could be detected between CaM expression in lesional skin and the studied clinical parameters of lichen planus patients.
UNASSIGNED: Tha main limitation of this study is its small sample size.
UNASSIGNED: CaM is upregulated in cutaneous lichen planus lesions suggesting a possible role in disease pathogenesis. Targeting CaM is expected to be a novel strategy for treatment of lichen planus.

OBJECTIVE: The single nucleotide polymorphism (SNP) rs12885713 of calmodulin 1 gene (CALM1) has been reported to involve in the etiology of osteoarthritis (OA) in several association studies with limited sample size and conflicting results. The purpose of the present systematic review and meta-analysis was to evaluate and synthesize the currently available data on the correlation between rs12885713 and OA susceptibility.
METHODS: Six electronic databases including PubMed, EMBASE, ISI Web of Science, CNETRAL, CNKI, and Wanfang were systematically retrieved to identify relevant observational articles published before October 2017. Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated to indicate the association between CALM1 polymorphism and OA. Risk of bias was assessed through the Newcastle-Ottawa Scale. Predetermined subgroups and sensitivity analyses were performed using the RevMan 5.3 software. Publication bias was evaluated by Egger and Begg tests.
RESULTS: Overall, 5 case-control studies involving 2183 OA patients 2654 healthy control subjects satisfied the meta-analysis. Recessive model was confirmed to be the best-matching genetic model (TT + TC versus CC). The pooled outcomes indicated that rs12885713 SNP was not significantly associated with OA vulnerability (OR 1.11, 95% CI 0.97, 1.27; P = .12). When stratified by different genders, OA sites, and population descents respectively, still non-significant associations were found.
CONCLUSIONS: Based on the findings of our present study, the rs12885713 polymorphism of CALM1 did not appear to be associated with OA predisposition.

To investigate the cyanylated cysteine vibrational probe group\'s ability to report on binding-induced changes along a protein-protein interface, the probe group was incorporated at several sites in a peptide of the calmodulin (CaM)-binding domain of skeletal muscle myosin light chain kinase. Isothermal titration calorimetry was used to determine the binding thermodynamics between calmodulin and each peptide. For all probe positions, the binding affinity was nearly identical to that of the unlabeled peptide. The CN stretching infrared band was collected for each peptide free in solution and bound to calmodulin. Binding-induced shifts in the IR spectral frequencies were correlated with estimated solvent accessibility based on molecular dynamics simulations. This work generally suggests (1) that site-specific incorporation of this vibrational probe group does not cause major perturbations to its local structural environment and (2) that this small probe group might be used quite broadly to map dynamic protein-binding interfaces. However, site-specific perturbations due to artificial labeling groups can be somewhat unpredictable and should be evaluated on a site-by-site basis through complementary measurements. A fully quantitative, simulation-based interpretation of the rich probe IR spectra is still needed but appears to be possible given recent advances in simulation techniques.

Primary cutaneous aspergillosis is a rare, life-threatening fungal infection in premature infants. We report a case of primary cutaneous aspergillosis caused by Aspergillus tamarii in an extremely low birthweight infant. The infant was delivered by cesarean section with complications from an intrauterine infection, brain intraventricular hemorrhage, tension pneumothorax and cardiac tamponade. On the 12th day of life, he developed erythematous maceration with erosion on his back. Septate hyphae were detected on two occasions from specimens of the skin lesion. The manifestations of the colony and slide culture showed the characteristics of A. tamarii. The nucleotide sequences of internal transcribed spacer regions of the ribosomal RNA gene, partial sequences of β-tubulin and calmodulin gene were compatible with those of A. tamarii. Of the known Aspergillus species, Aspergillus fumigatus and Aspergillus flavus have been reported in previous studies as the major causative agents in primary cutaneous aspergillosis, whereas human infection by A. tamarii is rare. We consider that A. tamarii is important as an unusual opportunistic human pathogen among premature infants.

The estrogen receptor α ligand-binding domain (ERα-LBD) binds the natural hormone 17β-estradiol (E2) to induce transcription and cell proliferation. This process occurs with the contribution of protein and peptide partners (also called coactivators) that can modulate the structure of ERα, and therefore its specificity of action. As with most transcription factors, ERα exhibits a high content of α helix, making it difficult to routinely run spectroscopic studies capable of deciphering the secondary structure of the different partners under binding conditions. Ca(2+)-calmodulin, a protein also highly structured in α-helix, is a key coactivator for ERα activity. Here, we show how circular dichroism can be used to study the interaction of ERα with Ca(2+)-calmodulin. Our approach allows the determination not only of the conformational changes induced upon complex formation but also the dissociation constant (K d) of this interaction.

The vast majority of vaginal fungal infections are caused by Candida species. However, vaginitis cases caused by molds are extremely rare. Aspergillus protuberus is previously known as a member of Aspergillus section Versicolores which can cause opportunistic infections in immunocompromised patients, however it has recently been described as a seperate species. Although the members of Aspergillus section Versicolores have been isolated rarely in cases of pulmonary infections, eye infections, otomycosis, osteomyelitis and onycomycoses, to the best of our knowledge, there is no published case of human infection caused by A.protuberus. In this report, the first case of persistent vaginitis due to A.protuberus in an immunocompetent patient was presented. A 42-year-old female patient was admitted to our hospital with the complaints of pelvic pain, vaginal itching and discharge during one month. Her symptoms had been persistant despite of the miconazole nitrate and clotrimazole therapies for probable candidal vaginitis. Fungal structures such as branched, septate hyphae together with the conidial forms were seen in microscopic examination as in the cervical smear. Thereafter, a vaginal discharge sample was taken for microbiological evaluation and similar characteristics of fungal structures were observed in the microscopic examination as of cervical smear. Then, preliminary result was reported as Aspergillus spp. At the same time, the sample was plated on Sabouraud dextrose agar (SDA) in duplicate and incubated at room temperature and at 37°C. After 5 days, white, powdery and pure-looking fungal colonies were observed in SDA which was incubated at room temperature, while the other medium remained sterile. The culture was submitted to the CBS-KNAW Fungal Biodiversity Center for further characterization. Phenotypic identification showed that the isolated strain belonged to the Aspergillus section Versicolores. The strain was grown for 7 days on malt extract agar and then ITS regions were amplified and sequenced from isolated DNA for genomic characterization. The obtained sequences were compared with the NCBI database and internal databases of the CBS-KNAW Fungal Biodiversity Centre and confirmed as Aspergillus section Versicolores. As a result of recent changes in classification of fungi, analysis of partial β-tubulin and calmodulin sequences have also been used to obtain a detailed and precise characterization. Eventually, the strain has been identified as A.protuberus which is a recently accepted species distinct from Aspergillus section Versicolores. As the patient could not be contacted after the preliminary report, detailed demographical information, probable origin and route of transmission of the agent and prognosis of infection remained obscure. In conclusion, the first case of vaginitis caused by A.protuberus was described in this report with the support of clinical, pathological, microbiological and molecular data.

Here we report the first crystal structure of a high-contrast genetically encoded circularly permuted green fluorescent protein (cpGFP)-based Ca(2+) sensor, Case16, in the presence of a low Ca(2+) concentration. The structure reveals the positioning of the chromophore within Case16 at the first stage of the Ca(2+)-dependent response when only two out of four Ca(2+)-binding pockets of calmodulin (CaM) are occupied with Ca(2+) ions. In such a \"half Ca(2+)-bound state\", Case16 is characterized by an incomplete interaction between its CaM-/M13-domains. We also report the crystal structure of the related Ca(2+) sensor Case12 at saturating Ca(2+) concentration. Based on this structure, we postulate that cpGFP-based Ca(2+) sensors can form non-functional homodimers where the CaM-domain of one sensor molecule binds symmetrically to the M13-peptide of the partner sensor molecule. Case12 and Case16 behavior upon addition of high concentrations of free CaM or M13-peptide reveals that the latter effectively blocks the fluorescent response of the sensor. We speculate that the demonstrated intermolecular interaction with endogenous substrates and homodimerization can impede proper functioning of this type of Ca(2+) sensors in living cells.