High-resolution solution structure of the EGF-like domain of heregulin-alpha.

The solution structure of the 63-residue heregulin-α (HRG-α) epidermal growth factor (EGF)-like domain, corresponding to residues 177−239 of HRG-α, has been determined to high resolution using data from two-dimensional and three-dimensional homo- and heteronuclear NMR spectroscopy. The structure is based on a total of 887 internuclear distance and dihedral restraints derived from data obtained using unlabeled and uniformly 15N-labeled protein samples, at pH 4.5, 20 °C. A total of 20 structures were calculated using a hybrid distance geometry−simulated annealing approach with the program DGII, followed by restrained molecular dynamics using the program DISCOVER. The average maximum violations are 0.12 ± 0.01 A and 1.4 ± 0.3° for distance and dihedral restraints, respectively. The backbone (N, Cα, C) atomic rms distribution about the mean coordinates for residues 3−23 and 31−49 is 0.29 ± 0.07 A. The N- and C-terminal residues (1−2 and 50−63) and the Ω-loop comprising residues 24−30 are disordered. Compariso...