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


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 alpha-aminobutyric acid (CH(2)-SH --> CH(2)-CH(3)). 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. Study holds ProTherm entries: 23670, 23671, 23672, 23673, 23674, 23675 Extra Details: The variant of IL-8 (residues 1-66) was used in this study intramolecular disulfides; conserved hydrophobic residues; receptor activity; packing interactions

Submission Details

ID: fcTxhFjX3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:54 p.m.

Version: 1

Publication Details
Rajagopalan L;Chin CC;Rajarathnam K,Biophys. J. (2007) Role of intramolecular disulfides in stability and structure of a noncovalent homodimer. PMID:17513351
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Interleukin-8 P10145 IL8_HUMAN
95.9 Interleukin-8 P67813 IL8_MACMU
95.9 Interleukin-8 P67814 IL8_MACNE
94.9 Interleukin-8 P46653 IL8_CERAT