Structure and Activity of a Chimeric Interleukin-8-Melanoma-Growth-Stimulatory-Activity Protein
| Autor: | Thomas Kirsch, Paul Rösch, Bettina Schmitt, Ivan J. D. Lindley, Markus Horcher, Heinrich Sticht, Jürgen Besemer, Manfred Auer |
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| Rok vydání: | 1996 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Neutrophils Protein Conformation Chemokine CXCL1 Recombinant Fusion Proteins Molecular Sequence Data In Vitro Techniques Transfection Biochemistry Protein Structure Secondary Cell Line Receptors Interleukin-8A Protein structure Antigens CD Humans Amino Acid Sequence Binding site Growth Substances Receptor Peptide sequence chemistry.chemical_classification Binding Sites Chemotactic Factors Molecular Structure Sequence Homology Amino Acid Chemistry Interleukin-8 Biological activity Receptors Interleukin Fusion protein Recombinant Proteins Amino acid Hexosaminidases Helix Intercellular Signaling Peptides and Proteins Thermodynamics Chemokines CXC |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1432-1033 0014-2956 |
| DOI: | 10.1111/j.1432-1033.1996.00026.x |
| Popis: | A 72-amino-acid chimeric protein, Chi1, was constructed from the N-terminal part of interleukin 8, IL-8-(1-53), and the C-terminal part of melanoma growth stimulatory activity, MGSA-(54-72). Chi1 protein showed receptor-binding specificity and biological activity similar, but not identical to IL-8 and decidedly different from MGSA. The structure of Chi1 was determined in solution by two-dimensional NMR and molecular-dynamics calculations. The structure resembled the structures of MGSA and IL-8 closely, containing a triple-stranded beta-sheet in the IL-8 part and an amphipathic alpha-helix in the MGSA part. Chi1 formed dimers at millimolar concentrations via the first strand from the N-terminus, analogous to IL-8 and MGSA. In contrast to the latter molecules, however, the alpha-helix of Chi1 did not pack against the beta-sheet part, but was an independent structural element. This structural difference could be explained mainly by the modulation of hydrophobic interactions between the helix and the rest of the protein in Chi1 as compared to IL-8 and MGSA. It is concluded that tight helix packing is not required for receptor binding and biological activity of Chi1. |
| Databáze: | OpenAIRE |
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