Structural modeling of protein-RNA complexes using crosslinking of segmentally isotope-labeled RNA and MS/MS

Nat Methods. 2017 May;14(5):487-490. doi: 10.1038/nmeth.4235. Epub 2017 Mar 27.

Abstract

Ribonucleoproteins (RNPs) are key regulators of cellular function. We established an efficient approach, crosslinking of segmentally isotope-labeled RNA and tandem mass spectrometry (CLIR-MS/MS), to localize protein-RNA interactions simultaneously at amino acid and nucleotide resolution. The approach was tested on polypyrimidine tract binding protein 1 and U1 small nuclear RNP. Our method provides distance restraints to support integrative atomic-scale structural modeling and to gain mechanistic insights into RNP-regulated processes.

MeSH terms

  • Binding Sites
  • Carbon Isotopes
  • Chromatography, High Pressure Liquid
  • Heterogeneous-Nuclear Ribonucleoproteins / chemistry*
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Models, Molecular*
  • Nitrogen Isotopes
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation*
  • Polypyrimidine Tract-Binding Protein / chemistry*
  • Polypyrimidine Tract-Binding Protein / genetics
  • Protein Binding
  • RNA / chemistry*
  • Ribonucleoprotein, U1 Small Nuclear / chemistry*
  • Ribonucleoprotein, U1 Small Nuclear / genetics
  • Software
  • Tandem Mass Spectrometry
  • Ultraviolet Rays

Substances

  • Carbon Isotopes
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nitrogen Isotopes
  • PTBP1 protein, human
  • Ribonucleoprotein, U1 Small Nuclear
  • Polypyrimidine Tract-Binding Protein
  • RNA