Projects per year
LMO2 was discovered via chromosomal translocations in T-cell leukaemia and shown normally to be essential for haematopoiesis. LMO2 is made up of two LIM only domains (thus it is a LIM-only protein) and forms a bridge in a multi-protein complex. We have studied the mechanism of formation of this complex using a single domain antibody fragment that inhibits LMO2 by sequestering it in a non-functional form. The crystal structure of LMO2 with this antibody fragment has been solved revealing a conformational difference in the positioning and angle between the two LIM domains compared with its normal binding. This contortion occurs by bending at a central helical region of LMO2. This is a unique mechanism for inhibiting an intracellular protein function and the structural contusion implies a model in which newly synthesized, intrinsically disordered LMO2 binds to a partner protein nucleating further interactions and suggests approaches for therapeutic targeting of LMO2.
|Publication status||Published - 10 Jan 2014|
- x-ray crystallography
- haematological cancer
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Narcis Fernandez Fuentes
- Faculty of Earth and Life Sciences, Institute of Biological, Environmental & Rural Sciences (IBERS) - Reader
Person: Teaching And Research
- 1 Finished
Bioinformatics and genomic and phenomic platform development
Armstead, I., Boyle, R., Doonan, J., Fernandez Fuentes, N., Gay, A., Hegarty, M., Huang, L., Neal, M., Swain, M. & Thomas, I.
Biotechnology and Biological Sciences Research Council
01 Apr 2012 → 31 Mar 2017
Project: Externally funded research