抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Organisms require an appropriate balance of stability and reversibility in gene expression programmes to maintain cell identity or to enable responses to stimuli; epigenetic regulation is integral to this dynamic control. Post-translational modification of histones by methylation is an important and widespread type of chromatin modification that is known to influence biological processes in the context of development and cellular responses. To evaluate how histone methylation contributes to stable or reversible control, we provide a broad overview of how histone methylation is regulated and leads to biological outcomes. The importance of appropriately maintaining or reprogramming histone methylation is illustrated by its links to disease and ageing and possibly to transmission of traits across generations.

/pdf/histone-methylation-a-dynamic-mark-in-health-disease-and-53e9mgdnmh.pdf

Histone methylation: a dynamic mark in health, disease and inheritance

Abscisic acid (ABA) is one of the “classical” plant hormones, i.e. discovered at least 50 years ago, that regulates many aspects of plant growth and development. This chapter reviews our current understanding of ABA synthesis, metabolism, transport, and signal transduction, emphasizing knowledge gained from studies of Arabidopsis. A combination of genetic, molecular and biochemical studies has identified nearly all of the enzymes involved in ABA metabolism, almost 200 loci regulating ABA response, and thousands of genes regulated by ABA in various contexts. Some of these regulators are implicated in cross-talk with other developmental, environmental or hormonal signals. Specific details of the ABA signaling mechanisms vary among tissues or developmental stages; these are discussed in the context of ABA effects on seed maturation, germination, seedling growth, vegetative stress responses, stomatal regulation, pathogen response, flowering, and senescence.

https://bioone.org/journals/the-arabidopsis-book/volume-2013/issue-11/tab.0166/Abscisic-Acid-Synthesis-and-Response/10.1199/tab.0166.pdf

Abscisic Acid synthesis and response.

Histone modifications are thought to regulate chromatin structure, transcription and other nuclear processes Histone methylation was originally believed to be an irreversible modification that could only be removed by histone eviction or by dilution during DNA replication However, the isolation of two families of enzymes that can demethylate histones has changed this notion The biochemical activities of these histone demethylases towards specific Lys residues on histones, and in some cases non-histone substrates, have highlighted their importance in developmental control, cell-fate decisions and disease Their ability to be regulated through protein-targeting complexes and post-translational modifications is also beginning to shed light on how they provide dynamic control during transcription

Molecular mechanisms and potential functions of histone demethylases.

Alzheimer’s disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4–3.5 A resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer’s disease. Filament cores are made of two identical protofilaments comprising residues 306–378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases. High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease. Alzheimer's disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. The lesions are made of paired helical and straight tau filaments (PHFs and SFs, respectively). Different tau filaments characterize other neurodegenerative diseases, suggesting that molecular conformers of aggregated tau underlie human tauopathies. No high-resolution structures of tau filaments are currently available. Here, Sjors Scheres and colleagues present cryo-electron microscopy (cryo-EM) maps at 3.5 A resolution and corresponding atomic models of PHFs and SFs from the brain of an individual with Alzheimer's disease. Their results show that cryo-EM enables atomic characterization of amyloid filaments from patient-derived material and could be used to study a range of neurodegenerative diseases.

Cryo-EM structures of tau filaments from Alzheimer's disease

https://www.cell.com/cell/pdf/S0092-8674(14)00721-1.pdf

Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

Complex structures of the abscisic acid receptor PYL3/RCAR13 reveal a unique regulatory mechanism.

Dynamic regulation of histone methylation/demethylation plays an important role during development. Mutations and truncations in human plant homeodomain (PHD) finger protein 8 (PHF8) are associated with X-linked mental retardation and facial anomalies, such as a long face, broad nasal tip, cleft lip/cleft palate and large hands, yet its molecular function and structural basis remain unclear. Here, we report the crystal structures of the catalytic core of PHF8 with or without α-ketoglutarate (α-KG) at high resolution. Biochemical and structural studies reveal that PHF8 is a novel histone demethylase specific for di- and mono-methylated histone H3 lysine 9 (H3K9me2/1), but not for H3K9me3. Our analyses also reveal how human PHF8 discriminates between methylation states and achieves sequence specificity for methylated H3K9. The in vitro demethylation assay also showed that the F279S mutant observed in clinical patients possesses no demethylation activity, suggesting that loss of enzymatic activity is crucial for pathogenesis of PHF8 patients. Taken together, these results will shed light on the molecular mechanism underlying PHF8-associated developmental and neurological diseases.

/pdf/structural-insights-into-a-novel-histone-demethylase-phf8-3v9ggdmcgq.pdf

Structural insights into a novel histone demethylase PHF8.

Metal hypersensitivity is a common immune disorder. Human immune systems mount the allergic attacks on metal ions through skin contacts, lung inhalation and metal-containing artificial body implants. The consequences can be simple annoyances to life-threatening systemic illness. Allergic hyper-reactivities to nickel (Ni) and beryllium (Be) are the best-studied human metal hypersensitivities. Ni-contact dermatitis affects 10 % of the human population, whereas Be compounds are the culprits of chronic Be disease (CBD). αβ T cells (T cells) play a crucial role in these hypersensitivity reactions. Metal ions work as haptens and bind to the surface of major histocompatibility complex (MHC) and peptide complex. This modifies the binding surface of MHC and triggers the immune response of T cells. Metal-specific αβ T cell receptors (TCRs) are usually MHC restricted, especially MHC class II (MHCII) restricted. Numerous models have been proposed, yet the mechanisms and molecular basis of metal hypersensitivity remain elusive. Recently, we determined the crystal structures of the Ni and Be presenting human MHCII molecules, HLA-DR52c (DRA*0101, DRB3*0301) and HLA-DP2 (DPA1*0103, DPB1*0201). These structures revealed unusual features of MHCII molecules and shed light on how metal ions are recognized by T cells.

Structural basis of metal hypersensitivity

Aims: The work is intended to achieve optimum culture conditions of α-galactosidase production by a mutant strain Penicillium sp. in solid-state fermentation (SSF).



Methods and Results:  Certain fermentation parameters involving incubation temperature, moisture content, initial pH value, inoculum and load size of medium, and incubation time were investigated separately. The optimal temperature and moisture level for α-galactosidase biosynthesis was found to be 30°C and 50%, respectively. The range of pH 5·5–6·5 was favourable. About 40–50 g of medium in 250-ml flask and inoculum over 1·0 × 106 spores were suitable for enzyme production. Seventy-five hours of incubation was enough for maximum α-galactosidase production. Substrate as wheat bran supplemented with soyabean meal and beet pulp markedly improved the enzyme yield in trays.



Conclusions:  Under optimum culture conditions, the α-galactosidase activity from Penicillium sp. MAFIC-6 indicated 185·2 U g−1 in tray of SSF.



Significant and Impact of the Study:  The process on α-galactosidase production in laboratory scale may have a potentiality of scaling-up.

Yang Wang

Papers

Structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.

Complex structures of the abscisic acid receptor PYL3/RCAR13 reveal a unique regulatory mechanism.

Structural insights into a novel histone demethylase PHF8.

Structural basis of metal hypersensitivity

Influence of cultivating conditions on the α-galactosidase biosynthesis from a novel strain of Penicillium sp. in solid-state fermentation