5N7E

Crystal structure of the Dbl-homology domain of Bcr-Abl in complex with monobody Mb(Bcr-DH_4).

5N7E の概要

• エントリーDOI: 10.2210/pdb5n7e/pdb
• 分子名称: Mb(Bcr-DH_4), Breakpoint cluster region protein (3 entities in total)
• 機能のキーワード: dbl-homology, monobody, bcr-abl, transferase, signaling protein
• 由来する生物種: synthetic construct; 詳細
• 細胞内の位置: Cell junction, synapse, postsynaptic cell membrane, postsynaptic density : P11274
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35022.68

構造登録者

Reckel, S.,Reynaud, A.,Pojer, F.,Hantschel, O. (登録日: 2017-02-20, 公開日: 2017-12-27, 最終更新日: 2024-01-17)

主引用文献

Reckel, S.,Gehin, C.,Tardivon, D.,Georgeon, S.,Kukenshoner, T.,Lohr, F.,Koide, A.,Buchner, L.,Panjkovich, A.,Reynaud, A.,Pinho, S.,Gerig, B.,Svergun, D.,Pojer, F.,Guntert, P.,Dotsch, V.,Koide, S.,Gavin, A.C.,Hantschel, O.
Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.
Nat Commun, 8:2101-2101, 2017

PubMed Abstract: The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.

PubMed: 29235475
DOI: 10.1038/s41467-017-02313-6

実験手法

X-RAY DIFFRACTION (1.647 Å)