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Publication Abstract from PubMed

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.

Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex.,Sewell H, Tanaka T, Omari KE, Mancini EJ, Cruz A, Fernandez-Fuentes N, Chambers J, Rabbitts TH Sci Rep. 2014 Jan 10;4:3643. doi: 10.1038/srep03643. PMID:24407558^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.