Sewell, H, Tanaka, T, Omari, K E, Mancini, E J, Cruz, A, Fernandez-Fuentes, N, Chambers, J and Rabbitts, T H (2014) Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex. Scientific Reports, 4. ISSN 2045-2322

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Abstract

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.

Item Type:	Article
Schools and Departments:	School of Life Sciences > Biochemistry
Subjects:	Q Science
Depositing User:	Tom Gittoes
Date Deposited:	30 Jan 2015 13:20
Last Modified:	06 Mar 2017 00:25
URI:	http://srodev.sussex.ac.uk/id/eprint/52548

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