2LMR

Solution structure of the first sam domain of odin

2LMR の概要

• エントリーDOI: 10.2210/pdb2lmr/pdb
• NMR情報: BMRB: 18134
• 分子名称: Ankyrin repeat and SAM domain-containing protein 1A (1 entity in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q92625
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11308.68

構造登録者

Leone, M.,Mercurio, F. (登録日: 2011-12-12, 公開日: 2012-03-14, 最終更新日: 2024-05-15)

主引用文献

Mercurio, F.A.,Marasco, D.,Pirone, L.,Pedone, E.M.,Pellecchia, M.,Leone, M.
Solution Structure of the First Sam Domain of Odin and Binding Studies with the EphA2 Receptor.
Biochemistry, 51:2136-2145, 2012

PubMed Abstract: The EphA2 receptor plays key roles in many physiological and pathological events, including cancer. The process of receptor endocytosis and the consequent degradation have attracted attention as possible means of overcoming the negative outcomes of EphA2 in cancer cells and decreasing tumor malignancy. A recent study indicates that Sam (sterile alpha motif) domains of Odin, a member of the ANKS (ankyrin repeat and sterile alpha motif domain-containing) family of proteins, are important for the regulation of EphA2 endocytosis. Odin contains two tandem Sam domains (Odin-Sam1 and -Sam2). Herein, we report on the nuclear magnetic resonance (NMR) solution structure of Odin-Sam1; through a variety of assays (employing NMR, surface plasmon resonance, and isothermal titration calorimetry techniques), we clearly demonstrate that Odin-Sam1 binds to the Sam domain of EphA2 in the low micromolar range. NMR chemical shift perturbation experiments and molecular modeling studies point out that the two Sam domains interact with a head-to-tail topology characteristic of several Sam-Sam complexes. This binding mode is similar to that we have previously proposed for the association between the Sam domains of the lipid phosphatase Ship2 and EphA2. This work further validates structural elements relevant for the heterotypic Sam-Sam interactions of EphA2 and provides novel insights for the design of potential therapeutic compounds that can modulate receptor endocytosis.

PubMed: 22332920
DOI: 10.1021/bi300141h

実験手法

SOLUTION NMR