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Experimental and theoretical studies of the three‐dimensional structure of human interleukin‐4
Author(s) -
Curtis Benson M.,
Presnell Scott R.,
Srinivasan Subhashini,
Sassenfeld Helmut,
Klinke Ralph,
Jeffery Eric,
Cosman David,
March Carl J.,
Cohen Fred E.
Publication year - 1991
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340110204
Subject(s) - antiparallel (mathematics) , circular dichroism , protein tertiary structure , protein secondary structure , crystallography , bundle , helix bundle , chemistry , helix (gastropod) , protein structure , structural motif , disulfide bond , stereochemistry , materials science , physics , biology , biochemistry , ecology , quantum mechanics , snail , magnetic field , composite material
The structure of human interleukin 4 (IL‐4) was predicted utilizing a series of experimental and theoretical techniques. Circular Dichroism (CD) spectroscopy indicated that IL‐4 belonged to the all α‐helix class of protein structures. Secondary structure prediction, site‐directed mutagenesis, and CD spectroscopy suggested a predominantly α‐helical structure, consistent with a four‐helix bundle structural motif. A human/mouse IL‐4 chimera was constructed to qualitatively evaluate alternative secondary structure predictions. The four predicted helices were assembled into tertiary structures using established algorithms. The mapping of three disulfide bridges in IL‐4 provided additional constraints on possible tertiary structures. Using accessible surface contact area as a criterion, the most suitable structures were right handed all antiparallel four‐helix bundles with two overhand loop connections. Successful loop closure and incorporation of the three disulfide constraints were possible while maintaining the expected shape, solvent accessibility, and steric interactions between loops and helices. Lastly, energy minimization was used to regularize the chain.