LOW RESOLUTION STRUCTURE OF INTERLEUKIN-1-BETA IN SOLUTION DERIVED FROM H-1-N-15 HETERONUCLEAR 3-DIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

A low resolution solution structure of the cytokine interleukin-1β, a 153 residue protein of molecular weight 17,400, has been determined on the basis of 446 nuclear Overhauser effect (NOE) derived approximate interproton distance restraints involving solely NH, CαH and CβH protons, supplemented by 90 distance restraints for 45 hydrogen bonds, and 79 φ torsion angle restraints. With the exception of 27 CαHCαH NOEs, all the NOEs were assigned from a three-dimensional 1H1H NOE 15N1H heteronuclear multiple quantum coherence (HMQC) spectrum. The torsion angle restraints were obtained from accurate 3JHNα coupling constants measured from a HMQC-J spectrum, while the hydrogen bonds were derived from a qualitative analysis of the NOE, coupling constant and amide exchange data. A total of 20 simulated annealing (SA) structures was computed using the hybrid distance geometry-dynamical simulated annealing method. The solution structure of IL-1β comprises 12 β-strands arranged in three pseudo-symmetrical topological units (each consisting of 5 anti-parallel β-strands), joined by turns, short loops and long loops. The core of the structure, which is made up of the 12 β-strands, together with the turns joining strands I and II, strands VIII and IX and strands X and XI, is well determined with a backbone atomic root-mean-square (r.m.s.) distribution about the mean co-ordinate positions of 1.2(± 0.1) Å. The loop conformations, on the other hand, are poorly determined by the current data. A comparison of the core of the low resolution solution structure of IL-1β with that of the X-ray structure indicates that they are similar, with a backbone atomic r.m.s. difference of only 1.5 Å between the co-ordinates of the restrained minimized mean of the SA structures and the X-ray structure. © 1990.