南加州大學的一個研究小組利用X射線晶體學的方法跟蹤大分子的運動,，首次觀察到了致癌蛋白LTag和關(guān)鍵的腫瘤抑制蛋白p53的結(jié)構(gòu),。每一個"罪惡"的LTag（large T antigen的縮寫）分子將六個p53捆綁起來，抑制它們的抑癌作用,，該研究發(fā)表了9月1日的《Genes & Development》上,。
有趣的是，p53蛋白通過阻止產(chǎn)生LTag病毒的復制來還擊,。勝負較強那一方?jīng)Q定,。
“假如你有許多功能性p53蛋白分子，你就可以制服LTag蛋白，” USC分子與計算生物學教授,，該研究的領導者Xiaojiang Chen說,。
“p53蛋白是一種非常重要的腫瘤抑制蛋白，在許多癌癥中均發(fā)生了突變,。”匹茲堡大學生物科學系教授James Pipas說,。
Pipas多年來從事LTag蛋白的研究，并且為它各種各樣的生物學功能感到驚奇,，包括高效的促癌作用等,，在他的一個演講中曾將LTag蛋白成為“宇宙中最令人驚奇的分子”,。
Pipas稱Chen的新研究為“一項非常重要的工作”,，展示了一個健康細胞的防御腫瘤的防線是怎樣瓦解的。
Pipas補充說,，該研究可能導致設計抗癌藥物的新技術(shù)的產(chǎn)生,。
Chen的研究小組通過將一個LTag和六個p53分子的復合體結(jié)晶，成功的描述了LTag 與 p53分子之間的相互作用,，它們之間一共存在著50,000個原子,。
Chen稱研究讓他重新看待LTag和LTag的“親代”——猿猴病毒 40（SV40）。SV40長期以來用作在培養(yǎng)細胞中誘導癌癥的研究工具,。
“不知道何故,，SV40知道p53分子的重要性，從而命令致癌蛋白LTag通過身體相互接觸作用靶向p53,，改變p53的構(gòu)象,。” Chen說。
假如SV40成功做到這一點,，結(jié)果就是新腫瘤產(chǎn)生了,。
英文原文：
Cell's fight against cancer revealed Cell's fight against cancer revealed
By the painstaking use of X-ray crystallography to track motion in very large molecules, a University of Southern California-led research group has taken a first look at the life-or-death struggle of a cancer-causing protein – LTag – and a key tumor suppressor – p53.
Each villainous LTag (short for large T antigen) single-handedly ties up a tag-team of six p53 molecules, inhibiting their tumor-suppressant role, the researchers report in the Sept. 1 issue of Genes & Development.
Undeterred, the p53 fight back by preventing replication of the virus that produces LTag, known as an oncoprotein for its function in cancer growth.
The champion depends on which side is stronger and healthier.
"If you have a lot of functional p53, you can override large T antigen," said lead researcher Xiaojiang Chen, professor in molecular and computational biology in the USC College of Letters, Arts and Sciences.
Sometimes called the "Guardian of the Genome," a damaged p53 can leave a cell almost defenseless.
"p53 is a very important tumor suppressor that's mutated in a vast majority of all cancers," said James Pipas, professor of biological sciences at the University of Pittsburgh.
It was Pipas who, after studying LTag for many years and marveling at its varied biological functions – including highly efficient tumor promotion – named it "The Most Amazing Molecule in the Universe" in one of his presentations.
Pipas called Chen's new study "a very important piece of work" that shows how a healthy cell's tumor defenses break down.
"Understanding exactly how this works is going to be a critical step toward our understanding of tumor genesis," he said.
This, in turn, may lead to new techniques for designing tumor-fighting drugs, Pipas added.
Chen's team was able to describe the interplay between LTag and p53 by crystallizing the complex of one LTag and six p53 molecules, totaling more than 50,000 atoms between them.
"It's quite a technical achievement, because these are fairly large proteins," Pipas said.
Chen said his study gave him new respect for LTag and its parent, Simian Virus 40. SV40 has long been used as a research tool to induce cancers in cell cultures.
"Somehow this virus knows how important p53 is, and has this oncoprotein (LTag) to target it by physically interacting with it and changing its conformation," Chen said.
If the virus succeeds, the result is a new tumor.
