PRC2蛋白质图像被首次捕获

一种与人类出生缺陷以及多种癌症相关的蛋白质复合体的详细完整图像被国际科学家领导的研究小组与美国能源部(DOE)劳伦斯伯克利国家实验室(Berkeley Lab)捕获。该物质，起始复合体蛋白2（Polycomb Repressive Complex 2）将为未来开发和改进治疗药物带来帮助。

Researchers obtain first detailed and complete picture of PRC2 protein

The first detailed and complete picture of a protein complex that is tied to human birth defects as well as the progression of many forms of cancer has been obtained by an international team of researchers led by scientists with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab). Knowing the architecture of this protein, PRC2, for Polycomb Repressive Complex 2, should be a boon to its future use in the development of new and improved therapeutic drugs.

"We present a complete molecular organization of human PRC2 that offers an invaluable structural context for understanding all of the previous biochemical and functional data that has been collected on this complex," says Berkeley Lab biophysicist Eva Nogales, an electron microscopy expert who led this research. "Our model should also be an invaluable tool for the design of new experiments aimed at asking detailed questions about the mechanisms that enable PRC2 to function and how those mechanisms might be exploited."

Nogales, who holds joint appointments with Berkeley Lab, the University of California (UC) at Berkeley, and the Howard Hughes Medical Institute (HHMI), is one of two corresponding authors of a paper describing this research in the journal eLife. The paper is titled "Molecular Architecture of Human Polycomb Repressive Complex 2." The other corresponding author is Claudio Cifferi, previously a postdoctoral fellow in the Nogales Lab, now with Novartis Vaccines and Diagnostic. Additional authors are Gabriel Lander, Alessio Maiolica, Franz Herzog and Ruedi Aebersold.

The link between PRC2 and embryonic development is well-established not just for humans but across the board for eukaryotic organisms. For example, studies with mice have shown that the deletion of any of PRC2's components results either in the death of an embryo or severe defects during the critical stages of early development. It is also well-established that PRC2 helps control the differentiation (specialization) of embryonic stem cells by acting to silence certain genetic messages with the nucleus of a cell.

"PRC2 controls stem cell differentiation by regulating the expression of specific genes through the binding and methylation of histones, the proteins in chromatin that help bundle DNA into nucleosomes," Nogales explains. "This is why PRC2 has been one of the top targets in drug development efforts by pharmaceutical companies."

Despite the numerous biochemical and molecular studies that have been done on PRC2, little has been known about the protein's overall architecture and the manner in which its different components interact to coordinate histone-binding and methylation. Nogales, Cifferi and their colleagues have closed this knowledge gap with their model, which they painstakingly constructed from data gathered via multiple sources including three-dimensional electron microscopy, mass spectrometry, protein biochemistry, crystal structure docking, and chemical cross-linking.