1H NMR solution structure of an active monomeric interleukin-8

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

Research output: Contribution to journalArticle

80 Citations (Scopus)

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 β sheet and a C-terminal α 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
StatePublished - 1995
Externally publishedYes

Fingerprint

Interleukin-8
Nuclear magnetic resonance
Monomers
Atoms
X-Rays
X rays
Dimerization
Simulated annealing
Interleukin-4
Disulfides
Nuclear magnetic resonance spectroscopy
Conformations
Proton Magnetic Resonance Spectroscopy
Magnetic Resonance Spectroscopy
Chemical activation
Geometry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rajarathnam, K., Clark-Lewis, I., & Sykes, B. D. (1995). 1H NMR solution structure of an active monomeric interleukin-8. Biochemistry, 34(40), 12983-12990.

1H NMR solution structure of an active monomeric interleukin-8. / Rajarathnam, Krishna; Clark-Lewis, Ian; Sykes, Brian D.

In: Biochemistry, Vol. 34, No. 40, 1995, p. 12983-12990.

Research output: Contribution to journalArticle

Rajarathnam, K, Clark-Lewis, I & Sykes, BD 1995, '1H NMR solution structure of an active monomeric interleukin-8', Biochemistry, vol. 34, no. 40, pp. 12983-12990.
Rajarathnam, Krishna ; Clark-Lewis, Ian ; Sykes, Brian D. / 1H NMR solution structure of an active monomeric interleukin-8. In: Biochemistry. 1995 ; Vol. 34, No. 40. pp. 12983-12990.
@article{0318032fc7b04a6f9b46585c3c1dcef2,
title = "1H NMR solution structure of an active monomeric interleukin-8",
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 {\AA} for the backbone atoms and 0.87 {\AA} for all heavy atoms. The structure consists of a series of turns and loops followed by a triple-stranded β sheet and a C-terminal α 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 {\AA} 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 {\AA}) and different from that seen in the dimeric NMR structure (rms difference 2.7 {\AA}). 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.",
author = "Krishna Rajarathnam and Ian Clark-Lewis and Sykes, {Brian D.}",
year = "1995",
language = "English (US)",
volume = "34",
pages = "12983--12990",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "40",

}

TY - JOUR

T1 - 1H NMR solution structure of an active monomeric interleukin-8

AU - Rajarathnam, Krishna

AU - Clark-Lewis, Ian

AU - Sykes, Brian D.

PY - 1995

Y1 - 1995

N2 - 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 β sheet and a C-terminal α 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.

AB - 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 β sheet and a C-terminal α 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.

UR - http://www.scopus.com/inward/record.url?scp=0028971068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028971068&partnerID=8YFLogxK

M3 - Article

VL - 34

SP - 12983

EP - 12990

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 40

ER -