Structure of the human Dicer-TRBP complex by electron microscopy
Pick-Wei Lau1, Clinton S Potter, Bridget Carragher
1National Resource for Automated Molecular Microscopy, The Scripps Institute, La Jolla, CA 92037, USA.
Structure (London, England : 1993)
|October 20, 2009
Summary
Researchers visualized the human Dicer-TRBP complex, revealing its L-shaped structure and a trench for binding double-stranded RNA (dsRNA). This provides insights into RNA interference (RNAi) initiation in multicellular organisms.
Area of Science:
- Molecular Biology
- Structural Biology
- Biochemistry
Background:
- Dicer is a crucial ribonuclease initiating RNA interference (RNAi).
- It processes double-stranded RNA (dsRNA) into small RNA fragments.
- Understanding Dicer's structure is key to RNAi mechanisms.
Purpose of the Study:
- To determine the three-dimensional structure of the human Dicer-TRBP complex.
- To elucidate the structural basis for dsRNA binding and RNAi initiation.
Main Methods:
- Negative-stain electron microscopy (EM) and single-particle analysis.
- Determination of the Dicer-TRBP complex structure at ~20 Å resolution.
- Computational docking of Giardia Dicer crystal structure into the EM map.
Main Results:
- The human Dicer-TRBP complex exhibits an L-shaped structure (150 Å x 100 Å).
- A surface trench along the long edge suggests a dsRNA-binding site.
- Two potential molecular architectures for human Dicer were proposed.
Conclusions:
- The study provides structural insights into human Dicer and its interaction with TRBP.
- The findings offer a framework for understanding the initiation of RNA interference.
- Structural data aids in comprehending Dicer function in multicellular organisms.
