Secondary structure and topology of interleukin-1 receptor antagonist protein determined by heteronuclear three-dimensional NMR spectroscopy

Interleukin-1 (IL-1) proteins, such as IL-1 beta, play a key role in immune and inflammatory responses. Interaction of these cytokines with the IL-1 receptor induces a variety of biological changes in neurologic, metabolic, hematologic, and endocrinologic systems. Interleukin-1 receptor antagonist p...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Easton) 1992-06, Vol.31 (23), p.5237-5245
Main Authors: Stockman, Brian J, Scahill, Terrence A, Roy, Melinda, Ulrich, Eldon L, Strakalaitis, Nancy A, Brunner, David P, Yem, Anthony W, Deibel, Martin R
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Humans
Hydrogen Bonding
In Vitro Techniques
Interleukin 1 Receptor Antagonist Protein
Magnetic Resonance Spectroscopy
Molecular biophysics
Molecular Sequence Data
Protein Conformation
Proteins - ultrastructure
Receptors, Immunologic - antagonists & inhibitors
Receptors, Interleukin-1
Recombinant Proteins
Sialoglycoproteins
Structure in molecular biology
Tridimensional structure
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Interleukin-1 (IL-1) proteins, such as IL-1 beta, play a key role in immune and inflammatory responses. Interaction of these cytokines with the IL-1 receptor induces a variety of biological changes in neurologic, metabolic, hematologic, and endocrinologic systems. Interleukin-1 receptor antagonist protein (IRAP) is a naturally occurring inhibitor of the interleukin-1 receptor. The 153-residue protein binds to the receptor with an affinity similar to that of IL-1 beta but does not elicit any physiological responses. As a first step toward understanding IRAP's mode of action, we have used multidimensional, heteronuclear NMR spectroscopy to determine the antagonist's solution secondary structure and global fold. Using a combination of 3D 1H-15N NOESY-HMQC and TOCSY-HMQC and 3D 1H-15N-13C HNCA and HN(CO)CA experiments on uniformly 15N- or doubly 13C/15N-enriched IRAP, we have made resonance assignments for more than 90% of the main-chain atoms. Analysis of short- and long-range NOE's indicates that IRAP is predominantly beta-sheet, with the same overall topology as IL-1 beta but with different regions of the primary sequence comprising the beta-strands. Two short helical segments also were identified. The 14% sequence identity between IL-1 beta and IRAP increases to 25% when differences in the locations of secondary structure elements in the primary sequences are taken into account. Still, numerous differences in side chains, which ultimately play a major role in receptor interaction, exist.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi00138a001