A Broad range of conformations contribute to the solution ensemble of the essential splicing factor U2AF(65)

Biochemistry. 2012 Jul 3;51(26):5223-5. doi: 10.1021/bi300277t. Epub 2012 Jun 19.

Abstract

U2AF(65) is essential for pre-mRNA splicing in most eukaryotes. Two consecutive RNA recognition motifs (RRM) of U2AF(65) recognize a polypyrimidine tract at the 3' splice site. Here, we use small-angle X-ray scattering to demonstrate that the tandem U2AF(65) RRMs exhibit a broad range of conformations in the solution ensemble. The majority of U2AF(65) conformations exhibit few contacts between the RRMs, such as observed in the crystal structure. A subpopulation adopts tight inter-RRM contacts, such as independently reported based on paramagnetic relaxation enhancements. These complementary structural methods demonstrate that diverse splice sites have the opportunity to select compact or extended inter-RRM proximities from the U2AF(65) conformational pool.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Splicing / physiology
  • Ribonucleoproteins / chemistry*
  • Ribonucleoproteins / metabolism
  • Solutions
  • Splicing Factor U2AF

Substances

  • Nuclear Proteins
  • Ribonucleoproteins
  • Solutions
  • Splicing Factor U2AF
  • U2AF2 protein, human