1zzp
From Proteopedia
(New page: 200px<br /> <applet load="1zzp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zzp" /> '''Solution structure of the F-actin binding d...) |
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'''Solution structure of the F-actin binding domain of Bcr-Abl/c-Abl'''<br /> | '''Solution structure of the F-actin binding domain of Bcr-Abl/c-Abl'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Bcr-Abl tyrosine kinase causes different forms of leukemia in humans. | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1ZZP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | + | 1ZZP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZZP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Guttler, T.]] | [[Category: Guttler, T.]] | ||
[[Category: Hantschel, O.]] | [[Category: Hantschel, O.]] | ||
| - | [[Category: Mackereth, C | + | [[Category: Mackereth, C D.]] |
[[Category: Mikes, Z.]] | [[Category: Mikes, Z.]] | ||
| - | [[Category: Rix, L | + | [[Category: Rix, L L.R.]] |
[[Category: Sattler, M.]] | [[Category: Sattler, M.]] | ||
[[Category: Superti-Furga, G.]] | [[Category: Superti-Furga, G.]] | ||
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[[Category: nuclear export signal]] | [[Category: nuclear export signal]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:20:42 2008'' |
Revision as of 14:20, 21 February 2008
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Solution structure of the F-actin binding domain of Bcr-Abl/c-Abl
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Leukemia, Philadelphia chromosome-positive, resistant to imatinib OMIM:[189980]
About this Structure
1ZZP is a Single protein structure of sequence from Homo sapiens. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl., Hantschel O, Wiesner S, Guttler T, Mackereth CD, Rix LL, Mikes Z, Dehne J, Gorlich D, Sattler M, Superti-Furga G, Mol Cell. 2005 Aug 19;19(4):461-73. PMID:16109371
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