5IH2

Structure, thermodynamics, and the role of conformational dynamics in the interactions between the N-terminal SH3 domain of CrkII and proline-rich motifs in cAbl

5IH2 の概要

• エントリーDOI: 10.2210/pdb5ih2/pdb
• 分子名称: Adapter molecule crk, Proline rich Peptide, DI(HYDROXYETHYL)ETHER, ... (6 entities in total)
• 機能のキーワード: sh3 domain polyproline ii motif, signaling protein
• 由来する生物種: Mus musculus (Mouse); 詳細
• 細胞内の位置: Cytoplasm : Q64010
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 17037.12

構造登録者

Bhatt, V.S.,Zeng, D.,Krieger, I.,Sacchettini, J.C.,Cho, J.-H. (登録日: 2016-02-28, 公開日: 2016-06-29, 最終更新日: 2024-10-30)

主引用文献

Bhatt, V.S.,Zeng, D.,Krieger, I.,Sacchettini, J.C.,Cho, J.H.
Binding Mechanism of the N-Terminal SH3 Domain of CrkII and Proline-Rich Motifs in cAbl.
Biophys.J., 110:2630-2641, 2016

PubMed Abstract: The N-terminal Src homology 3 (nSH3) domain of a signaling adaptor protein, CT-10 regulator of kinase II (CrkII), recognizes proline-rich motifs (PRMs) of binding partners, such as cAbl kinase. The interaction between CrkII and cAbl kinase is involved in the regulation of cell spreading, microbial pathogenesis, and cancer metastasis. Here, we report the detailed biophysical characterizations of the interactions between the nSH3 domain of CrkII and PRMs in cAbl. We identified that the nSH3 domain of CrkII binds to three PRMs in cAbl with virtually identical affinities. Structural studies, by using x-ray crystallography and NMR spectroscopy, revealed that the binding modes of all three nSH3:PRM complexes are highly similar to each other. Van 't Hoff analysis revealed that nSH3:PRM interaction is associated with favorable enthalpy and unfavorable entropy change. The combination of experimentally determined thermodynamic parameters, structure-based calculations, and (15)N NMR relaxation analysis highlights the energetic contribution of conformational entropy change upon the complex formation, and water molecules structured in the binding interface of the nSH3:PRM complex. Understanding the molecular basis of nSH3:PRM interaction will provide, to our knowledge, new insights for the rational design of small molecules targeting the interaction between CrkII and cAbl.

PubMed: 27332121
DOI: 10.1016/j.bpj.2016.05.008

実験手法

X-RAY DIFFRACTION (1.8 Å)