@article{484fbda317954dde8dddc0be2a234c5a,
title = "Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl",
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 αIII 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.",
author = "Oliver Hantschel and Silke Wiesner and Thomas G{\"u}ttler and MacKereth, {Cameron D.} and Rix, {Lily L.Remsing} and Zsuzsanna Mikes and Jana Dehne and Dirk G{\"o}rlich and Michael Sattler and Giulio Superti-Furga",
note = "Funding Information: We thank the Frankfurt DFG/NMR 900 MHz center; the European Molecular Biology Laboratory (EMBL)/Heidelberg and Institute of Molecular Pathology/Vienna confocal microscopy facilities; G. Stier for advice; M. Way, K. Djinovic-Carugo, and V. Small for reading of the manuscript; and K. Dorey for the Xenopus sequence. This work was supported by fellowships from the EMBL (O.H.), European Molecular Biology Organization (C.D.M.), German Research Foundation DFG (S.W.), Aventis (O.H.), Boehringer Ingelheim Fonds (T.G.), and the Leukemia and Lymphoma Society (L.L.R.R.). Work in the participating labs is funded by the EMBL, the Austrian Academy of Sciences, and the DFG. ",
year = "2005",
month = aug,
day = "19",
doi = "10.1016/j.molcel.2005.06.030",
language = "English",
volume = "19",
pages = "461--473",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}