University of Sussex
Browse
Sewell_et_al_(2014).pdf (1.57 MB)

Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex

Download (1.57 MB)
journal contribution
posted on 2023-06-08, 19:50 authored by H Sewell, T Tanaka, K E Omari, Erika ManciniErika Mancini, A Cruz, N Fernandez-Fuentes, J Chambers, T H Rabbitts
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Scientific Reports

ISSN

2045-2322

Publisher

Nature Publishing Group

Issue

1

Volume

4

Article number

a3643

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Haematology Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2015-01-30

First Open Access (FOA) Date

2015-01-30

First Compliant Deposit (FCD) Date

2015-01-30

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC