The solution structure of Abl SH3, and its relationship to SH2 in the SH(32) construct

Structure
Y Q GosserD Cowburn

Abstract

The Src homology domains, SH3 and SH2, of Abl protein tyrosine kinase regulate enzymatic activity in vivo. Abl SH3 suppresses kinase activity, whereas Abl SH2 is required for the transforming activity of the activated form of Abl. We expect that the solution structures of Abl SH3, Abl SH2 and Abl SH(32) (a dual domain comprising SH3 and SH2 subdomains) will contribute to a structural basis for understanding the mechanism of the Abl 'regulatory apparatus'. We present the solution structure of the free Abl SH3 domain and a structural characterization of the Abl regulatory apparatus, the SH(32) dual domain. The solution structure of Abl SH3 was determined using multidimensional double resonance NMR spectroscopy. It consists of two antiparallel beta sheets packed orthogonally, an arrangement first shown in spectrin SH3. Compared with the crystal structure of the Abl SH3 complexed with a natural ligand, there is no significant difference in overall folding pattern. The structure of the Abl SH(32) dual domain was characterized by NMR spectroscopy using the 1H and 15N resonance assignment of Abl SH3 and Abl SH2. On the basis of the high degree of similarity in chemical shifts and hydrogen/deuterium exchange pattern for the individual ...Continue Reading

References

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Citations

Jan 1, 1997·Biopolymers·D C DalgarnoR J Rickles
Oct 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Logan W DonaldsonJulie D Forman-Kay
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y OdaB T Chait
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·R XuT W Muir
Jan 1, 1997·Annual Review of Biophysics and Biomolecular Structure·J Kuriyan, D Cowburn
Feb 21, 2006·Journal of Molecular Biology·Thomas E Wales, John R Engen
Jul 11, 2006·Magnetic Resonance in Chemistry : MRC·Hong JiDavid Cowburn
Jul 18, 2002·Structure·Tobias S UlmerIain D Campbell
Mar 25, 2008·Archives of Biochemistry and Biophysics·Katja PetzoldLars Backman
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Sep 15, 2000·Journal of Molecular Biology·K N BrazinA H Andreotti
Feb 17, 2001·Journal of Molecular Biology·S YuzawaF Inagaki

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