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 language||English (US)|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Molecular Biology