2JXC

Structure of the EPS15-EH2 Stonin2 Complex

2JXC の概要

• エントリーDOI: 10.2210/pdb2jxc/pdb
• 関連するPDBエントリー: 1eh2 1ff1
• NMR情報: BMRB: 15554
• 分子名称: Epidermal growth factor receptor substrate 15, Stonin-2, CALCIUM ION (3 entities in total)
• 機能のキーワード: endocytosis, membrane, phosphorylation, proto-oncogene, sh3-binding, endocytosis-protein binding complex, endocytosis/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm. Isoform 2: Early endosome membrane; Peripheral membrane protein; Cytoplasmic side: P42566; Cytoplasm: Q8WXE9
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 16005.18

構造登録者

Rumpf, J.,Simon, B.,Jung, N.,Maritzen, T.,Haucke, V.,Sattler, M.,Groemping, Y. (登録日: 2007-11-12, 公開日: 2008-01-08, 最終更新日: 2024-05-01)

主引用文献

Rumpf, J.,Simon, B.,Jung, N.,Maritzen, T.,Haucke, V.,Sattler, M.,Groemping, Y.
Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity.
Embo J., 27:558-569, 2008

PubMed Abstract: Eps15 homology (EH) domain-containing proteins play a key regulatory role in intracellular membrane trafficking and cell signalling. EH domains serve as interaction platforms for short peptide motifs comprising the residues NPF within natively unstructured regions of accessory proteins. The EH-NPF interactions described thus far are of very low affinity and specificity. Here, we identify the presynaptic endocytic sorting adaptor stonin2 as a high-affinity ligand for the second EH domain (EH2) of the clathrin accessory protein Eps15. Calorimetric data indicate that both NPF motifs within stonin2 interact with EH2 simultaneously and with sub-micromolar affinity. The solution structure of this complex reveals that the first NPF motif binds to the conserved site on the EH domain, whereas the second motif inserts into a novel hydrophobic pocket. Our data show how combination of two EH-attachment sites provides a means for modulating specificity and allows discrimination from a large pool of potential binding partners containing NPF motifs.

PubMed: 18200045
DOI: 10.1038/sj.emboj.7601980

実験手法

SOLUTION NMR