5N6R
Solution structure of the Dbl-homology domain of Bcr-Abl
Summary for 5N6R
| Entry DOI | 10.2210/pdb5n6r/pdb |
| NMR Information | BMRB: 34101 |
| Descriptor | Breakpoint cluster region protein (1 entity in total) |
| Functional Keywords | dbl-homology, helical bundle, bcr-abl, leukemia, transferase, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 24844.43 |
| Authors | Reckel, S.,Lohr, F.,Buchner, L.,Guntert, P.,Dotsch, V.,Hantschel, O. (deposition date: 2017-02-16, release date: 2017-12-27, Last modification date: 2024-06-19) |
| 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 Cited by 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: 29235475DOI: 10.1038/s41467-017-02313-6 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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