Role of intramolecular disulfides in stability and structure of a noncovalent homodimer

Lavanya Rajagopalan, Christopher C. Chin, Krishna Rajarathnam

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The importance of intramolecular disulfides in a noncovalent dimeric protein interleukin-8 (IL-8) has been studied by replacing cysteines in each of the two disulfide pairs with α-aminobutyric acid (CH2-SH → CH2-CH3). Both disulfide mutants are less stable and exist as molten globules in the monomeric state. Interestingly, both mutants dimerize, though with slightly lower affinities compared to the native protein. NMR studies suggest a molten globule-like structure also in the dimeric state. Structures, sequence analysis, and mutagenesis studies have shown that the conserved hydrophobic residues are packed against each other in the protein core and that H bonding and van der Waals interactions stabilize the dimer interface. Deleting either disulfide in IL-8 results in substantial loss in receptor activity, indicating that both disulfides are critical for function in the folded protein. These data together suggest that the packing interactions of the hydrophobic core determine IL-8 monomer fold, that disulfides play only a marginal role in dimer formation, and that the stability imparted by the disulfides is intimately coupled to fold and function.

Original languageEnglish (US)
Pages (from-to)2129-2134
Number of pages6
JournalBiophysical Journal
Volume93
Issue number6
DOIs
StatePublished - Sep 2007

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Disulfides
Interleukin-8
Proteins
Aminobutyrates
Hydrophobic and Hydrophilic Interactions
Mutagenesis
Cysteine
Sequence Analysis

ASJC Scopus subject areas

  • Biophysics

Cite this

Role of intramolecular disulfides in stability and structure of a noncovalent homodimer. / Rajagopalan, Lavanya; Chin, Christopher C.; Rajarathnam, Krishna.

In: Biophysical Journal, Vol. 93, No. 6, 09.2007, p. 2129-2134.

Research output: Contribution to journalArticle

Rajagopalan, Lavanya ; Chin, Christopher C. ; Rajarathnam, Krishna. / Role of intramolecular disulfides in stability and structure of a noncovalent homodimer. In: Biophysical Journal. 2007 ; Vol. 93, No. 6. pp. 2129-2134.
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