study of possible interdomain interactions in an Abl SH32 dual domain construct by solution NMR technique

R. Xn, D. Fushman, Sean M. Cahill, Q. Xu, David Cowburn

Research output: Contribution to journalArticle

Abstract

The proto orirogerie proclurt, Abl, hat several individually folded domains. Experiments suggest that these domains mediate its signal transduction interactivelv. The SH3 of Abl appears to suppress the intrinsic transforming ability, while its SH2 is absolutely required for expression of the transforming activity of activated Abl. The SHlt and SH2 domains may not have direct intramolecular interaction with each other in Abl, however, the topological folding of these two closely located domains max still strongly affect the formation of a regulatory complex, Tim solution stiurture of the free SH32 dual domains of Abl. and the one wiih a consolidated ligand mimicing its possible down regulation stale, lias b<>en studied by NMR. The relative orientation of two domains is revealed. The structure shows very limited intramolecular interaction between the two domains. The linker region between these two domains is still very flexible even with a consolidated ligand bound to both domains. However. Abl SH32 apparently partially dimerizes at concentration above 100 uM, through intennoienilar heterodomain interaction. The interaction is specific. Both SH3 and SH2 binding peptides can dramaticaîlv reduce (his interaction. Finally, the structural information provides insight for designing more tightly bound lifiands. whkh may have potential therapeutic value to block 1 he transforming activity of Hticoprotein Abl.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number8
StatePublished - 1998
Externally publishedYes

Fingerprint

Nuclear magnetic resonance
Ligands
Signal transduction
src Homology Domains
signal transduction
Signal Transduction
Down-Regulation
peptides
therapeutics
Peptides
methodology
Experiments
ligands
Therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

study of possible interdomain interactions in an Abl SH32 dual domain construct by solution NMR technique. / Xn, R.; Fushman, D.; Cahill, Sean M.; Xu, Q.; Cowburn, David.

In: FASEB Journal, Vol. 12, No. 8, 1998.

Research output: Contribution to journalArticle

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AU - Cowburn, David

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