Structure of the Bcr-Abl oncoprotein oligomerization domain.
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Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS
Structure of the Bcr-Abl oncoprotein oligomerization domain.
Nat Struct Biol. 2002 Feb;9(2):117-20.
- PubMed ID
- 11780146 [ View in PubMed]
- Abstract
The Bcr-Abl oncoprotein is responsible for a wide range of human leukemias, including most cases of Philadelphia chromosome-positive chronic myelogenous leukemia. Oligomerization of Bcr-Abl is essential for oncogenicity. We determined the crystal structure of the N-terminal oligomerization domain of Bcr-Abl (residues 1-72 or Bcr1-72) and found a novel mode of oligomer formation. Two N-shaped monomers dimerize by swapping N-terminal helices and by forming an antiparallel coiled coil between C-terminal helices. Two dimers then stack onto each other to form a tetramer. The Bcr1-72 structure provides a basis for the design of inhibitors of Bcr-Abl transforming activity by disrupting Bcr-Abl oligomerization.