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

Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

Tissue-based map of the human proteome

Recent advances in next-generation DNA sequencing and proteomics provide an unprecedented ability to survey mRNA and protein abundances. Such proteome-wide surveys are illuminating the extent to which different aspects of gene expression help to regulate cellular protein abundances. Current data demonstrate a substantial role for regulatory processes occurring after mRNA is made - that is, post-transcriptional, translational and protein degradation regulation - in controlling steady-state protein abundances. Intriguing observations are also emerging in relation to cells following perturbation, single-cell studies and the apparent evolutionary conservation of protein and mRNA abundances. Here, we summarize current understanding of the major factors regulating protein expression.

/pdf/insights-into-the-regulation-of-protein-abundance-from-1nb4o968ef.pdf

Insights into the regulation of protein abundance from proteomic and transcriptomic analyses

基礎講座 電気泳動(Electrophoresis)

On the Dependency of Cellular Protein Levels on mRNA Abundance.

Protein and messenger RNA (mRNA) copy numbers vary from cell to cell in isogenic bacterial populations. However, these molecules often exist in low copy numbers and are difficult to detect in single cells. We carried out quantitative system-wide analyses of protein and mRNA expression in individual cells with single-molecule sensitivity using a newly constructed yellow fluorescent protein fusion library for Escherichia coli. We found that almost all protein number distributions can be described by the gamma distribution with two fitting parameters which, at low expression levels, have clear physical interpretations as the transcription rate and protein burst size. At high expression levels, the distributions are dominated by extrinsic noise. We found that a single cell's protein and mRNA copy numbers for any given gene are uncorrelated.

/pdf/quantifying-e-coli-proteome-and-transcriptome-with-single-1xqg8lgkev.pdf

Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells.

https://www.jstage.jst.go.jp/article/biophys/51/3/51_3_136/_pdf

Quantifying E. coli Proteome and Transcriptome with Single-molecule Sensitivity in Single Cells

Kinesin is a stepping motor that successively produces forward and backward 8-nm steps along microtubules. Under physiological conditions, the steps powering kinesin's motility are biased in one direction and drive various biological motile processes. The physical mechanism underlying the unidirectional bias of the kinesin steps is not fully understood. Here we explored the mechanical kinetics and thermodynamics of forward and backward kinesin steps by analyzing their temperature and load dependence. Results show that the frequency asymmetry between forward and backward steps is produced by entropy. Furthermore, the magnitude of the entropic asymmetry is 6 k(B)T, more than three times greater than expected from a current model, in which a mechanical conformational change within the kinesin molecular structure directly biases the kinesin steps forward. We propose that the stepping direction of kinesin is preferably caused by an entropy asymmetry resulting from the compatibility between the kinesin and microtubule interaction based on their polar structures.

Entropy rectifies the Brownian steps of kinesin.

Sub-nucleosomal Genome Structure Reveals Distinct Nucleosome Folding Motifs.

Movement is a fundamental characteristic of all living things. This biogenic function that is attributed to the molecular motors such as kinesin, dynein and myosin. Molecular motors generate forces by using chemical energy derived from the hydrolysis reaction of ATP molecules. Despite a large number of studies on this topic, the chemomechanical energy transduction mechanism is still unsolved. In this study, we have investigated the chemomechanical coupling of the ATPase cycle to the mechanical events of the molecular motor kinesin using single molecule detection (SMD) techniques. The SMD techniques allowed to detection of the movement of single kinesin molecules along a microtubule and showed that kinesin steps mainly in the forward direction, but occasionally in the backward. The stepping direction is determined by a certain load-dependent process, on which the stochastic behavior is well characterized by Feynman's thermal ratchet model. The driving force of the stepwise movement is essentially Brownian motion, but it is biased in the forward direction by using the free energy released from the hydrolysis of ATP.

Yuichi Taniguchi

Papers

Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells.

Quantifying E. coli Proteome and Transcriptome with Single-molecule Sensitivity in Single Cells

Entropy rectifies the Brownian steps of kinesin.

Sub-nucleosomal Genome Structure Reveals Distinct Nucleosome Folding Motifs.

Single molecule processes on the stepwise movement of ATP-driven molecular motors