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PDBsum entry 4kfz
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Transcription
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PDB id
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4kfz
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References listed in PDB file
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Key reference
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Title
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Conformational flexibility of the oncogenic protein lmo2 primes the formation of the multi-Protein transcription complex.
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Authors
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H.Sewell,
T.Tanaka,
K.El omari,
E.J.Mancini,
A.Cruz,
N.Fernandez-Fuentes,
J.Chambers,
T.H.Rabbitts.
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Ref.
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Sci Rep, 2014,
4,
3643.
[DOI no: ]
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PubMed id
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Abstract
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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.
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