Structural highlights
4kfz is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| Gene: | LMO2, RBTN2, RBTNL1, RHOM2, TTG2 (HUMAN), Anti-LMO2 VH (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[RBTN2_HUMAN] A chromosomal aberration involving LMO2 may be a cause of a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(11,14)(p13;q11) with TCRD.
Function
[RBTN2_HUMAN] Acts with TAL1/SCL to regulate red blood cell development. Also acts with LDB1 to maintain erythroid precursors in an immature state.
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.
References
- ↑ Sewell H, Tanaka T, Omari KE, Mancini EJ, Cruz A, Fernandez-Fuentes N, Chambers J, Rabbitts TH. Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex. Sci Rep. 2014 Jan 10;4:3643. doi: 10.1038/srep03643. PMID:24407558 doi:http://dx.doi.org/10.1038/srep03643
