Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy

Robert Powers, Daniel S. Garrett, Carl J. March, Eric A. Frieden, Angela M. Gronenborn, G. Marius Clore

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

The three-dimensional solution structure of recombinant human interleukin-4, a protein of 133 residues and 15.4 kilodaltons that plays a key role in the immune and inflammatory systems, has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substantial differences in the relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone-extracellular receptor complex.

Original languageEnglish (US)
Pages (from-to)1673-1677
Number of pages5
JournalScience
Volume256
Issue number5064
DOIs
StatePublished - Jan 1 1992

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Somatotropin Receptors
Cell Surface Receptors
Granulocyte-Macrophage Colony-Stimulating Factor
Sequence Homology
Crystallization
Interleukin-4
Disulfides
Growth Hormone
Immune System
Magnetic Resonance Spectroscopy
Proteins
human IL4 protein

ASJC Scopus subject areas

  • General

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Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. / Powers, Robert; Garrett, Daniel S.; March, Carl J.; Frieden, Eric A.; Gronenborn, Angela M.; Clore, G. Marius.

In: Science, Vol. 256, No. 5064, 01.01.1992, p. 1673-1677.

Research output: Contribution to journalArticle

Powers, Robert ; Garrett, Daniel S. ; March, Carl J. ; Frieden, Eric A. ; Gronenborn, Angela M. ; Clore, G. Marius. / Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. In: Science. 1992 ; Vol. 256, No. 5064. pp. 1673-1677.
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