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

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00123a032· OSTI ID:5562592
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  1. Tokyo Metropolitan Inst. of Medical Science (Japan)
  2. Otsuka Pharmaceutical Co., Ltd., Tokushima (Japan)
  3. JEOL, Inc., Tokyo (Japan)
  4. Japan Womens College, Tokyo (Japan)

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, {sup 15}N 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 {sup 15}N-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 which forms the receptor-binding site of IL-1{beta}.

OSTI ID:
5562592
Journal Information:
Biochemistry; (United States), Vol. 31:8; ISSN 0006-2960
Country of Publication:
United States
Language:
English