TCR-induced sumoylation… 都啥玩意儿啊,咋读啊?(1)

由于老师们的时间安排的关系,第一次文献阅读会的主题文献是篇不太好读的关于免疫的分子机制的研究。但大家不用担心,首先在线上我会尽量引导大家,下周的组会(具体通知可能要过几天敲定细节后再发)上也会有一定的讲解、讨论时间,所以放轻松读即可。
PS:论文链接为http://www.nature.com/ni/journal/v16/n11/full/ni.3259.html ,群文件中有pdf.


TCR-induced sumoylation of the kinase PKC-θ controls T cell synapse organization and T cell activation

从标题可以大概看出,这篇文章主要内容就是TCR对PKC-θ的sumoylation在T细胞的synapse organization和activation中的作用。估计大多数同学已经满脸问号了,陌生的东西太多,我们慢慢看。

SUMOylation

如果有同学已经对化学物质的英文命名比较了解的话,就会看出这个词的意思是SUMO化,也就是给接上一个SUMO基团。那SUMO是啥?

Small Ubiquitin-like Modifier (or SUMO) proteins are a family of small proteins that are covalently attached to and detached from other proteins in cells to modify their function.

来,划词翻译走起~ 顺便提一句,据我所知比较好的划词翻译工具有欧路词典、必应词典、灵格斯等

接下来,SUMO蛋白都是咋接到目标上的呢?

Attachment: SUMO attachment to its target is similar to that of ubiquitin. The SUMO precursor has some extra aminoacids that need to be removed, therefore a C-terminal peptide is cleaved from the SUMO precursor by a protease to reveal a di-glycine motif. The obtained SUMO then becomes bound to an E1 enzyme (SUMO Activating Enzyme (SAE)) which is a heterodimer. It is then passed to an E2 which is a conjugating enzyme (Ubc9). Finally, one of a small number of E3 ligating proteins attaches it to the protein.

看晕了?不要紧,记得SUMO E3 ligating proteins就好。

如果你想知道更多的话……(这部分可以跳过)

Functions: protein stability, nuclear-cytosolic transport, and transcriptional regulation.

Typically, only a small fraction of a given protein is SUMOylated and this modification is rapidly reversed by the action of deSUMOylating enzymes.

Differents: There are 4 confirmed SUMO isoforms in humans; SUMO-1, SUMO-2, SUMO-3 and SUMO-4. SUMO-2/3 show a high degree of similarity to each other and are distinct from SUMO-1. SUMO-4 shows similarity to SUMO-2/3 but differs in having a Proline instead of Glutamine at position 90. As a result, SUMO-4 isn't processed and conjugated under normal conditions, but is used for modification of proteins under stress-conditions like starvation. During mitosis, SUMO-2/3 localize to centromeres and condensed chromosomes, whereas SUMO-1 localizes to the mitotic spindle and spindle midzone, indicating that SUMO paralogs regulate distinct mitotic processes in mammalian cells.

Structure: SUMO proteins are small; most are around 100 amino acids in length and 12 kDa in mass.Although SUMO has very little sequence identity with ubiquitin at the amino acid level, it has a nearly identical structural fold.

TCR、PKC-θ、T cell synapse organization & activation

偷个懒,这些东西是什么及它们之间的关系在这篇paper的Introduction里讲得很清楚,而且不难懂,加持着划词翻译的你一定能看懂的,真有地方看不懂可以来打我问我。
想看到他们长什么样?这里有些图

synapse抽象画
不需要看懂的通路图

当然了,不是完全不需要看懂,不过只要看得出信号是从TCR-CD3复合体和CD28共同的stimulation到PKC-θ再到NF-κB等一票因子,就够去读我们的文献了。

对呀对呀,文献到底说了些啥?李迎秋老师到底在Nature Immunology上搞了什么大新闻?别急,读完上面的东西,你肯定已经能读懂我们可爱的主题文献的Introduction了,它会告诉你李老师工作成果的大致情况,以及这项研究解决了什么科学问题。等你读完了,我可要拿上面的问题问你哦~

好了,我已经写不动了相信一路读下来你也已经累了,好好休息会先吧~如果你觉得自己已经搞定了Introduction,为自己鼓个掌吧

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