This complex plays a key role in the RNA interference (RNAi) pathway that silences gene expression. Describing the molecular structure of a eukaryotic Argonaute protein has been a goal of the RNAi field for close to a decade.
"You can learn a lot from biochemical experiments, but to more fully understand a protein like Argonaute, it's useful to know where all of the atoms are and which amino acids are playing important roles," says Whitehead Institute Member David Bartel, who is also an MIT professor of biology and a Howard Hughes Medical Institute (HHMI) investigator. "Learning the Argonaute crystal structure is an important step in understanding the RNAi biochemical pathway and will be the basis for many future experiments."
The yeast Argonaute structure is described in the June 21st print issue of Nature.
In humans and most other eukaryotes, the RNAi pathway can reduce cellular protein production by reducing the proteins' RNA templates. By exploiting this pathway, scientists are able to knock down the expression of specific proteins and thereby determine their roles within the cell or organism. The RNAi pathway has also been of considerable interest for the treatment of human disease.
RNAi depends on two proteins, Dicer and Argonaute. Dicer recognizes double-stranded RNA (dsRNA), latches onto it, and chops it into pieces 21-23 nucleotides long. Argonaute recognizes the dsRNA bits, discards one strand, and uses the other as a guide. When a single-stranded RNA matches the guide RNA's sequence, Argonaute cleaves the targeted RNA, thereby preventing it from serving as a template for protein production.
To determine the structure of Argonaute, Bartel and graduate student David Weinberg partnered with Kotaro Nakanishi in Dinshaw Patel's lab at Sloan-Kettering. Although the team expected to solve the structure of Argonaute alone, they were surprised to find that the protein came along with small bits of RNA that were also observed in the structure. The incorporation of these RNAs had switched the protein into an activated state that contained a four-component active site, the identification of which solved a longstanding mystery of what constituted the "missing" fourth component. With the structure of this complex in hand, scientists now have a better understanding for how it works.
"Seeing the crystal structure of a eukaryotic Argonaute for the first time was very exciting—it's such a large protein with a complicated topology and many moving parts," says Weinberg. "It's a really impressive molecular machine."
This work was supported by National Institutes of Health (NIH), the Human Frontier Science Program, the Japan Society for the Promotion of Science, and the National Science Foundation (NSF).
Written by Nicole Giese Rura
David Bartel is a Member at Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Investigator and a professor of biology at Massachusetts Institute of Technology.
"Structure of yeast Argonaute with guide RNA"
Nature. June 21, 2012.
Kotaro Nakanishi (1,4), David E. Weinberg (2,3,4), David P. Bartel (2,3) & Dinshaw J. Patel (1).1. Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
4. These authors contributed equally to this work.
Nicole Giese Rura | EurekAlert!
Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo
Full of hot air and proud of it
18.04.2018 | University of Pittsburgh
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.
Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
19.04.2018 | Materials Sciences
19.04.2018 | Physics and Astronomy
19.04.2018 | Physics and Astronomy