1H NMR Solution Structure of an Active Monomeric Interleukin-8

Krishnakumar Rajarathnam, Ian Clark-Lewis, Brian D. Sykes

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

The solution structure of a monomeric form of interleukin-8 (IL-8) has been solved using 1H NMR spectroscopy. The chemically synthesized nonnatural analog {IL-8 (4-72) L25 NH → NCH3} has the same activity as that of native IL-8. Thirty structures were generated using the hybrid distance geometry and simulated annealing protocol using the program X-PLOR. The structure is well-defined except for N-terminal residues 4-6 and C-terminal residues 67-72. The rms distribution about the average structure for residues 7-66 is 0.38 Å for the backbone atoms and 0.87 Å for all heavy atoms. The structure consists of a series of turns and loops followed by a triple-stranded sheet and a C-terminal a helix. The structure of the monomer is largely similar to the native dimeric IL-8 structures previously determined by both NMR and X-ray methods. The major difference is that, in the monomeric analog, the C-terminal residues 67-72 are disordered whereas they are helical in the two dimeric structures. The best fit superposition of the backbone atoms of residues 7-66 of the monomer structure on the dimeric IL-8 structures showed rms differences of 1.5 and 1.2 Å respectively. The turn (residues 31-35), which is disulfide linked to the N-terminal region, adopts a conformation in the monomer similar to that seen in the dimeric X-ray structure (rms difference 1.4 Å) and different from that seen in the dimeric NMR structure (rms difference 2.7 Å). The structural data indicate that the constraints imposed by dimerization are not critical either for the tertiary fold or for functional activation of IL-8.

Original languageEnglish (US)
Pages (from-to)12983-12990
Number of pages8
JournalBiochemistry
Volume34
Issue number40
DOIs
StatePublished - Oct 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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