Experimental and theoretical studies of the three-dimensional structure of human interleukin-4

Autor: Carl J. March, Curtis Benson M, Ralph Klinke, Subhashini Srinivasan, Fred E. Cohen, Scott R. Presnell, David Cosman, Helmut Sassenfeld, Eric Jeffery
Rok vydání: 1991
Předmět:
Zdroj: Proteins: Structure, Function, and Genetics. 11:111-119
ISSN: 1097-0134
0887-3585
Popis: 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 alpha-helix class of protein structures. Secondary structure prediction, site-directed mutagenesis, and CD spectroscopy suggested a predominantly alpha-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.
Databáze: OpenAIRE
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