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 |
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Rok vydání: | 1991 |
Předmět: |
Models
Molecular Steric effects Circular dichroism Protein Conformation Chemistry Circular Dichroism Molecular Sequence Data Exons Antiparallel (biochemistry) Energy minimization Biochemistry Crystallography Protein structure Structural Biology Bundle Mutagenesis Site-Directed Humans Amino Acid Sequence Disulfides Interleukin-4 Structural motif Molecular Biology Protein secondary structure Chromatography High Pressure Liquid |
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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