5N7E

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

Summary for 5N7E

• Entry DOI: 10.2210/pdb5n7e/pdb
• Descriptor: Mb(Bcr-DH_4), Breakpoint cluster region protein (3 entities in total)
• Functional Keywords: dbl-homology, monobody, bcr-abl, transferase, signaling protein
• Biological source: synthetic construct; More
• Cellular location: Cell junction, synapse, postsynaptic cell membrane, postsynaptic density : P11274
• Total number of polymer chains: 2
• Total formula weight: 35022.68

Authors

Reckel, S.,Reynaud, A.,Pojer, F.,Hantschel, O. (deposition date: 2017-02-20, release date: 2017-12-27, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.647 Å)