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

Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases.

/pdf/non-muscle-myosin-ii-takes-centre-stage-in-cell-adhesion-and-3fxem36lz2.pdf

Non-muscle myosin II takes centre stage in cell adhesion and migration.

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

Interactome networks and human disease

https://www.cell.com/cell/pdf/S0092-8674(13)00573-4.pdf

Forces in Tissue Morphogenesis and Patterning

The dynamic behaviour of myosin V molecules translocating along actin filaments has been mainly studied by optical microscopy. The processive hand-over-hand movement coupled with hydrolysis of adenosine triphosphate was thereby demonstrated. However, the protein molecules themselves are invisible in the observations and have therefore been visualized by electron microscopy in the stationary states. The concomitant assessment of structure and dynamics has been unfeasible, a situation prevailing throughout biological research. Here we directly visualize myosin V molecules walking along actin tracks, using high-speed atomic force microscopy. The high-resolution movies not only provide corroborative 'visual evidence' for previously speculated or demonstrated molecular behaviours, including lever-arm swing, but also reveal more detailed behaviours of the molecules, leading to a comprehensive understanding of the motor mechanism. Our direct and dynamic high-resolution visualization is a powerful new approach to studying the structure and dynamics of biomolecules in action.

/pdf/video-imaging-of-walking-myosin-v-by-high-speed-atomic-force-4mvtywgxgl.pdf

Video imaging of walking myosin V by high-speed atomic force microscopy

Loads on molecular motors regulate and coordinate their function. In a study that directly measures properties of internally strained myosin 2 heads bound to actin, we find that human nonmuscle myosins 2A and 2B show marked load-dependent changes in kinetics of ADP release but not in nucleotide binding. We show that the ADP release rate constant is increased 4-fold by the assisting load on one head and decreased 5-fold (for 2A) or 12-fold (for 2B) by the resisting load on the other. Thus these myosins, especially 2B, have marked mechanosensitivity of product release. By regulating the actin attachment of myosin heads, this provides a basis for energy-efficient tension maintenance without obstructing cellular contractility driven by other motors such as smooth muscle myosin. Whereas forward load accelerates the cycle of interaction with actin, resistive load increases duty ratio to favor tension maintenance by two-headed attachment.

https://www.pnas.org/content/pnas/104/24/9994.full.pdf

Load-dependent mechanism of nonmuscle myosin 2

The success of chemotherapy lies in the continuous search for new drugs to counter the challenge posed by resistant strains. Methanol extracts of six plant species traditionally used in Indian folklore medicine for the treatment of various bacterial and fungal infections were investigated for in vitro antimicrobial activity against pathogens namely Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger by disc diffusion method. Methanol extracts of Eugenia jambolana and Cassia auriculata showed the highest toxicity against all the bacteria. The plant extracts showed antibacterial activity but not antifungal activity against any of the fungi used. Minimum inhibitory concentration (MIC) assay were determined for these two extracts against bacteria. E. jambolana revealed the highest antimicrobial activity at a minimum concentration (0.75 mg/ml) against S. aureus. The phytochemical analysis carried out revealed the presence of coumarins, flavanoids, glycosides, phenols, tannins, saponins and steroids. Alkaloids were not detected from any of the plant extracts under study. The results provide justification for the use of the plants in folk medicine to treat various infectious diseases.

/pdf/antimicrobial-activity-and-phytochemical-analysis-of-j6qqsr6ele.pdf

Antimicrobial activity and phytochemical analysis of selected Indian folk medicinal plants

Myosin 5 is a two-headed motor protein that moves cargoes along actin filaments. Its tail ends in paired globular tail domains (GTDs) thought to bind cargo. At nanomolar calcium levels, actin-activated ATPase is low and the molecule is folded. Micromolar calcium concentrations activate ATPase and the molecule unfolds. Here we describe the structure of folded myosin and the GTD's role in regulating activity. Electron microscopy shows that the two heads lie either side of the tail, contacting the GTDs at a lobe of the motor domain (approximately Pro 117-Pro 137) that contains conserved acidic side chains, suggesting ionic interactions between motor domain and GTD. Myosin 5 heavy meromyosin, a constitutively active fragment lacking the GTDs, is inhibited and folded by a dimeric GST-GTD fusion protein. Motility assays reveal that at nanomolar calcium levels heavy meromyosin moves robustly on actin filaments whereas few myosins bind or move. These results combine to show that with no cargo, the GTDs bind in an intramolecular manner to the motor domains, producing an inhibited and compact structure that binds weakly to actin and allows the molecule to recycle towards new cargoes.

The cargo-binding domain regulates structure and activity of myosin 5

http://biophys.w3.kanazawa-u.ac.jp/References/Myosin%20V/M5CaReg-Wang-JBC-2004.pdf

Kavitha Thirumurugan

Papers

Load-dependent mechanism of nonmuscle myosin 2

Antimicrobial activity and phytochemical analysis of selected Indian folk medicinal plants

The cargo-binding domain regulates structure and activity of myosin 5

Regulated Conformation of Myosin V

The predicted coiled-coil domain of myosin 10 forms a novel elongated domain that lengthens the head.