Stable isotope aided nuclear magnetic resonance study to investigate the receptor-binding site of human interleukin 1 beta

Biochemistry. 1992 Mar 3;31(8):2435-42. doi: 10.1021/bi00123a032.

Abstract

Resonance assignments for interleukin 1 beta at neutral pH were made by using three-dimensional NMR in combination with specific labeling and double-labeling methods with stable isotopes. On the basis of the present assignments, 15N single-quantum coherence spectra of N-terminal truncated and fusion mutants were compared with that of the wild-type. Although these mutants have reduced biological activity, they showed 15N-SQC spectra similar to that of the wild-type. However, small but significant chemical shift changes were observed for amino acid residues within a loop 86-99, in spite of the modification at the N-terminus, supporting the idea that this loop forms a biologically active part of interleukin 1 beta. Receptor-binding activity was studied for mutants (Asp-93)-, (Leu-93)- and des-(Arg-98)interleukin 1 beta's. The results show significant loss of the receptor-binding activity. The N-terminus, the C-terminus, and the loop 86-99 form a part of the open end of a beta-barrel [Finzel, B. C., Clancy, L. L., Holland, D. R., Muchmore, S. W., Watenpaugh, K. D., & Einspahr, H. M. (1989) J. Mol. Biol. 209, 779-791; Clore, G. M., Wingfield, P. T., & Gronenborn, A. M. (1991) Biochemistry 30, 2315-2323], which forms the receptor-binding site of IL-1 beta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry
  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cricetinae
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-1 / chemistry*
  • Interleukin-1 / genetics
  • Interleukin-1 / isolation & purification
  • Magnetic Resonance Spectroscopy / methods
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Nitrogen Isotopes
  • Protein Binding
  • Protein Conformation
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / isolation & purification
  • Receptors, Interleukin-1
  • Solutions
  • Water

Substances

  • Amides
  • Interleukin-1
  • Nitrogen Isotopes
  • Receptors, Immunologic
  • Receptors, Interleukin-1
  • Solutions
  • Water