1HAF

HEREGULIN-ALPHA EPIDERMAL GROWTH FACTOR-LIKE DOMAIN, NMR, MINIMIZED AVERAGE STRUCTURE

Summary for 1HAF

• Entry DOI: 10.2210/pdb1haf/pdb
• Descriptor: HEREGULIN-ALPHA (1 entity in total)
• Functional Keywords: growth factor
• Biological source: Homo sapiens (human)
• Cellular location: Pro-neuregulin-1, membrane-bound isoform: Cell membrane; Single-pass type I membrane protein. Neuregulin-1: Secreted. Isoform 8: Nucleus. Isoform 9: Secreted. Isoform 10: Membrane; Single-pass type I membrane protein: Q02297
• Total number of polymer chains: 1
• Total formula weight: 7129.22

Authors

Jacobsen, N.E.,Skelton, N.J.,Fairbrother, W.J. (deposition date: 1995-11-30, release date: 1996-07-11, Last modification date: 2024-11-20)

Primary citation

Jacobsen, N.E.,Abadi, N.,Sliwkowski, M.X.,Reilly, D.,Skelton, N.J.,Fairbrother, W.J.
High-resolution solution structure of the EGF-like domain of heregulin-alpha.
Biochemistry, 35:3402-3417, 1996

PubMed Abstract: The solution structure of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain, corresponding to residues 177-239 of HRG-alpha, 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 degrees 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 angstroms and 1.4 +/- 0.3 degrees for distance and dihedral restraints, respectively. The backbone (N,C(alpha),C) atomic rms distribution about the mean coordinates for residues 3-23 and 31-49 is 0.29 +/- 0/07 angstroms. The N-and C-terminal residues (1-2 and 50-63) and 24-30 are disordered. Comparison of the HRG-alpha EGF-like domain structure with the previously determined structure of human EGF [Hommel et al. (1992) J. Mol. Biol. 227, 271-282] reveals a high degree of structural similarity; excluding the N-terminal region (residues 1-13), the disordered phi-loop region (residues 24-30) that contains a three-residue insertion in HRG-alpha relative to hEGF, and the disordered C-terminal region (residues 50-63), the C(alpha) alignment between the HRG-alpha and hEGF minimized mean structures has a rms difference of approximately 1 angstrom. In HRG-alpha the N-terminal residues 2-6 form a well-defined beta strand rather than being disordered as found for hEGF. This structural difference correlates with functional data which suggest that the N-terminal region of the HRG-alpha EGF-like domain is responsible for the observed receptor specificity differences between HRG-alpha and EGF.

PubMed: 8639490
DOI: 10.1021/bi952626l

Experimental method

SOLUTION NMR