Determination of the secondary structure and folding topology of human interleukin-4 using three-dimensional heteronuclear magnetic resonance spectroscopy

Biochemistry. 1992 May 5;31(17):4347-53. doi: 10.1021/bi00132a027.


The secondary structure of human recombinant interleukin-4 (IL-4) has been investigated by three-dimensional (3D) 15N- and 13C-edited nuclear Overhauser (NOE) spectroscopy on the basis of the 1H, 15N, and 13C assignments presented in the preceding paper [Powers, R., Garrett, D. S., March, C. J., Frieden, E. A., Gronenborn, A. M., & Clore, G. M. (1992) Biochemistry (preceding paper in this issue)]. Based on the NOE data involving the NH, C alpha H, and C beta H protons, as well as 3JHN alpha coupling constant, amide exchange, and 13C alpha and 13C beta secondary chemical shift data, it is shown that IL-4 consists of four long helices (residues 9-21, 45-64, 74-96, and 113-129), two small helical turns (residues 27-29 and 67-70), and a mini antiparallel beta-sheet (residues 32-34 and 110-112). In addition, the topological arrangement of the helices and the global fold could be readily deduced from a number of long-range interhelical NOEs identified in the 3D 13C-edited NOE spectrum in combination with the spatial restrictions imposed by three disulfide bridges. These data indicate that the helices of interleukin-4 are arranged in a left-handed four-helix bundle with two overhand connections.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Disulfides
  • Humans
  • Hydrogen Bonding
  • Interleukin-4 / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Recombinant Proteins


  • Disulfides
  • Recombinant Proteins
  • Interleukin-4