Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1994 Aug 1;13(15):3517-23.
doi: 10.1002/j.1460-2075.1994.tb06658.x.

Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4

K Nagata  1 , D Kohda, H Hatanaka, S Ichikawa, S Matsuda, T Yamamoto, A Suzuki, F Inagaki
Affiliations

Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4

K Nagata et al. EMBO J. .

Abstract

p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. J Mol Biol. 1986 Oct 5;191(3):523-51 - PubMed
    1. FEBS Lett. 1992 May 4;302(1):39-42 - PubMed
    1. Science. 1989 Feb 24;243(4894 Pt 1):1074-6 - PubMed
    1. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9836-40 - PubMed
    1. FEBS Lett. 1990 Feb 26;261(2):392-6 - PubMed

Publication types