1HRF

SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4

1HRF の概要

• エントリーDOI: 10.2210/pdb1hrf/pdb
• 分子名称: HEREGULIN ALPHA (1 entity in total)
• 機能のキーワード: growth factor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: 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
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7544.69

構造登録者

Nagata, K.,Kohda, D.,Hatanaka, H.,Ichikawa, S.,Inagaki, F. (登録日: 1994-07-21, 公開日: 1994-10-15, 最終更新日: 2024-10-23)

主引用文献

Nagata, K.,Kohda, D.,Hatanaka, H.,Ichikawa, S.,Matsuda, S.,Yamamoto, T.,Suzuki, A.,Inagaki, F.
Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.
EMBO J., 13:3517-3523, 1994

PubMed 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: 8062828

実験手法

SOLUTION NMR