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Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions
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Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions

Published on: September 28, 2017

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Crystal and solution structures of human oncoprotein Musashi-2 N-terminal RNA recognition motif 1

Lan Lan1, Minli Xing2, Maithri Kashipathy3

  • 1Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas.

Proteins
|October 12, 2019
PubMed

Insights

Researchers determined the structure of Musashi-2 RNA binding protein (MSI2-RRM1) using crystal and NMR methods. This structural data aids in understanding MSI2-RNA interactions and designing targeted cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Musashi-2 (MSI2) is an RNA binding protein overexpressed in various cancers.
  • MSI2, like MSI1, plays a role in posttranscriptional gene regulation and is a therapeutic target.
  • Existing MSI1 inhibitors also bind MSI2, necessitating MSI2-specific drug design.

Purpose of the Study:

  • To elucidate the structure of the MSI2 RNA recognition motif 1 (MSI2-RRM1).
  • To compare the MSI2-RRM1 structure with MSI1-RBD1 and other RNA binding proteins.
  • To provide structural insights for developing MSI2-specific inhibitors.

Main Methods:

  • X-ray crystallography to determine the crystal structure of MSI2-RRM1.
  • Nuclear Magnetic Resonance (NMR) spectroscopy to determine the solution structure of MSI2-RRM1.
  • Comparative structural analysis of MSI2-RRM1, MSI1-RBD1, and other RNA binding proteins.

Main Results:

  • The crystal structure and the first NMR solution structure of MSI2-RRM1 were successfully determined.
  • High structural similarity was observed between the crystal and NMR solution structures.
  • MSI2-RRM1 exhibits a folding topology highly similar to MSI1-RBD1 and other RNA binding proteins.

Conclusions:

  • The determined structures of MSI2-RRM1 provide valuable insights into MSI2-RNA interactions.
  • This structural information is crucial for the rational drug design of novel MSI2-specific inhibitors.
  • Understanding MSI2 structure can lead to more effective targeted cancer therapies.
Keywords:
MusashiRNA-binding pocketRNA-binding proteincrystallographynuclear magnetic resonance

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