1ZZP

Solution structure of the F-actin binding domain of Bcr-Abl/c-Abl

Summary for 1ZZP

• Entry DOI: 10.2210/pdb1zzp/pdb
• NMR Information: BMRB: 6570
• Descriptor: Proto-oncogene tyrosine-protein kinase ABL1 (1 entity in total)
• Functional Keywords: four helix bundle, nuclear export signal, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton. Isoform IB: Nucleus membrane; Lipid-anchor: P00519
• Total number of polymer chains: 1
• Total formula weight: 14150.12

Authors

Hantschel, O.,Wiesner, S.,Guttler, T.,Mackereth, C.D.,Rix, L.L.R.,Mikes, Z.,Dehne, J.,Gorlich, D.,Sattler, M.,Superti-Furga, G. (deposition date: 2005-06-14, release date: 2005-08-30, Last modification date: 2024-05-22)

Primary citation

Hantschel, O.,Wiesner, S.,Guttler, T.,Mackereth, C.D.,Rix, L.L.R.,Mikes, Z.,Dehne, J.,Gorlich, D.,Sattler, M.,Superti-Furga, G.
Structural Basis for the Cytoskeletal Association of Bcr-Abl/c-Abl.
Mol.Cell, 19:461-473, 2005

PubMed Abstract: 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.

PubMed: 16109371
DOI: 10.1016/j.molcel.2005.06.030

Experimental method

SOLUTION NMR