1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in interleukin-8

Krishna Rajarathnam, Ian Clark-Lewis, Beatrice Dewald, Marco Baggiolini, Brian D. Sykes

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

In order to assess the importance of the buried Glu-38 observed in the structure of interleukin-8, an analog in which Glu-38 was replaced with Ala (E38A analog) was investigated by 1H NMR spectroscopy and neutrophil activation. Detailed analysis of the NMR NOESY data showed that the solution structure of the E38A analog is essentially the same as that for the native protein. Also, the neutrophil elastase activity of the E38A analog was similar to that of the native protein. However, the Gln-8 and Cys-9 amide proton chemical shifts, which are significantly downfield-shifted in the native protein, exhibit more 'normal' values. This observation indicates that in the native protein, Glu-38 side-chain carboxylate interacts with Gln-8 and Cys-9 amide protons. Although the N-terminal residues are critical for function, this interaction is not essential for neutrophil activation.

Original languageEnglish (US)
Pages (from-to)43-46
Number of pages4
JournalFEBS Letters
Volume399
Issue number1-2
DOIs
StatePublished - Dec 9 1996
Externally publishedYes

Fingerprint

Interleukin-8
Nuclear magnetic resonance
Neutrophil Activation
Amides
Protons
Proteins
Chemical activation
Leukocyte Elastase
Chemical shift
Nuclear magnetic resonance spectroscopy
Reference Values
Magnetic Resonance Spectroscopy
Proton Magnetic Resonance Spectroscopy

Keywords

  • Chemokine
  • H-bonding interaction
  • Interleukin-8
  • NMR
  • Structure-function

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in interleukin-8. / Rajarathnam, Krishna; Clark-Lewis, Ian; Dewald, Beatrice; Baggiolini, Marco; Sykes, Brian D.

In: FEBS Letters, Vol. 399, No. 1-2, 09.12.1996, p. 43-46.

Research output: Contribution to journalArticle

Rajarathnam, Krishna ; Clark-Lewis, Ian ; Dewald, Beatrice ; Baggiolini, Marco ; Sykes, Brian D. / 1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in interleukin-8. In: FEBS Letters. 1996 ; Vol. 399, No. 1-2. pp. 43-46.
@article{4ec4a17dc1544a42a4e6598a5297c662,
title = "1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in interleukin-8",
abstract = "In order to assess the importance of the buried Glu-38 observed in the structure of interleukin-8, an analog in which Glu-38 was replaced with Ala (E38A analog) was investigated by 1H NMR spectroscopy and neutrophil activation. Detailed analysis of the NMR NOESY data showed that the solution structure of the E38A analog is essentially the same as that for the native protein. Also, the neutrophil elastase activity of the E38A analog was similar to that of the native protein. However, the Gln-8 and Cys-9 amide proton chemical shifts, which are significantly downfield-shifted in the native protein, exhibit more 'normal' values. This observation indicates that in the native protein, Glu-38 side-chain carboxylate interacts with Gln-8 and Cys-9 amide protons. Although the N-terminal residues are critical for function, this interaction is not essential for neutrophil activation.",
keywords = "Chemokine, H-bonding interaction, Interleukin-8, NMR, Structure-function",
author = "Krishna Rajarathnam and Ian Clark-Lewis and Beatrice Dewald and Marco Baggiolini and Sykes, {Brian D.}",
year = "1996",
month = "12",
day = "9",
doi = "10.1016/S0014-5793(96)01277-X",
language = "English (US)",
volume = "399",
pages = "43--46",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - 1H NMR evidence that Glu-38 interacts with the N-terminal functional domain in interleukin-8

AU - Rajarathnam, Krishna

AU - Clark-Lewis, Ian

AU - Dewald, Beatrice

AU - Baggiolini, Marco

AU - Sykes, Brian D.

PY - 1996/12/9

Y1 - 1996/12/9

N2 - In order to assess the importance of the buried Glu-38 observed in the structure of interleukin-8, an analog in which Glu-38 was replaced with Ala (E38A analog) was investigated by 1H NMR spectroscopy and neutrophil activation. Detailed analysis of the NMR NOESY data showed that the solution structure of the E38A analog is essentially the same as that for the native protein. Also, the neutrophil elastase activity of the E38A analog was similar to that of the native protein. However, the Gln-8 and Cys-9 amide proton chemical shifts, which are significantly downfield-shifted in the native protein, exhibit more 'normal' values. This observation indicates that in the native protein, Glu-38 side-chain carboxylate interacts with Gln-8 and Cys-9 amide protons. Although the N-terminal residues are critical for function, this interaction is not essential for neutrophil activation.

AB - In order to assess the importance of the buried Glu-38 observed in the structure of interleukin-8, an analog in which Glu-38 was replaced with Ala (E38A analog) was investigated by 1H NMR spectroscopy and neutrophil activation. Detailed analysis of the NMR NOESY data showed that the solution structure of the E38A analog is essentially the same as that for the native protein. Also, the neutrophil elastase activity of the E38A analog was similar to that of the native protein. However, the Gln-8 and Cys-9 amide proton chemical shifts, which are significantly downfield-shifted in the native protein, exhibit more 'normal' values. This observation indicates that in the native protein, Glu-38 side-chain carboxylate interacts with Gln-8 and Cys-9 amide protons. Although the N-terminal residues are critical for function, this interaction is not essential for neutrophil activation.

KW - Chemokine

KW - H-bonding interaction

KW - Interleukin-8

KW - NMR

KW - Structure-function

UR - http://www.scopus.com/inward/record.url?scp=0030577240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030577240&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(96)01277-X

DO - 10.1016/S0014-5793(96)01277-X

M3 - Article

VL - 399

SP - 43

EP - 46

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 1-2

ER -