Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl

Mol Cell. 2005 Aug 19;19(4):461-73. doi: 10.1016/j.molcel.2005.06.030.


The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. Depending on its position within the cell, Bcr-Abl differentially affects cellular growth. However, no structural and molecular details for the anticipated localization determinants are available. We present the NMR structure of the F-actin binding domain (FABD) of Bcr-Abl and its cellular counterpart c-Abl. The FABD forms a compact left-handed four-helix bundle in solution. We show that the nuclear export signal (NES) previously reported in this region is part of the hydrophobic core and nonfunctional in the intact protein. In contrast, we could identify the critical residues of helix alphaIII that are responsible for F-actin binding and cytoskeletal association. We propose that these interactions represent a major determinant for both Bcr-Abl and c-Abl localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cytoskeleton / metabolism*
  • Fusion Proteins, bcr-abl / chemistry*
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Microfilament Proteins / chemistry*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nucleocytoplasmic Transport Proteins / chemistry
  • Nucleocytoplasmic Transport Proteins / genetics
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-abl / chemistry*
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism
  • Sequence Homology, Amino Acid


  • Actins
  • Carrier Proteins
  • F-actin-binding proteins
  • Microfilament Proteins
  • Nucleocytoplasmic Transport Proteins
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl

Associated data

  • PDB/1ZZP