4KFZ

Crystal structure of LMO2 and anti-LMO2 VH complex

4KFZ の概要

• エントリーDOI: 10.2210/pdb4kfz/pdb
• 分子名称: LMO-2, Anti-LMO2 VH, ZINC ION (3 entities in total)
• 機能のキーワード: oncoprotein, t-cell leukemia, proto-oncogene, transcription, developmental protein, lim domain, transcription factor, nucleus
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus (Potential): P25791
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 63620.93

構造登録者

Sewell, H.,Tanaka, T.,El Omari, K.,Cruz-Migoni, A.,Mancini, E.J.,Fuentes-Fernandez, N.,Chambers, J.,Rabbitts, T.H. (登録日: 2013-04-28, 公開日: 2014-01-22, 最終更新日: 2023-09-20)

主引用文献

Sewell, H.,Tanaka, T.,Omari, K.E.,Mancini, E.J.,Cruz, A.,Fernandez-Fuentes, N.,Chambers, J.,Rabbitts, T.H.
Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex.
Sci Rep, 4:3643-3643, 2014

PubMed 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.

PubMed: 24407558
DOI: 10.1038/srep03643

実験手法

X-RAY DIFFRACTION (2.8 Å)