School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia.
Protein Sci. 2012 Nov;21(11):1768-74. doi: 10.1002/pro.2153. Epub 2012 Sep 25.
LIM-only protein 2, Lmo2, is a regulatory protein that is essential for hematopoietic development and inappropriate overexpression of Lmo2 in T-cells contributes to T-cell leukemia. It exerts its functions by mediating protein-protein interactions and nucleating multicomponent transcriptional complexes. Lmo2 interacts with LIM domain binding protein 1 (Ldb1) through the tandem LIM domains of Lmo2 and the LIM interaction domain (LID) of Ldb1. Here, we present the solution structure of the LIM2 domain of Lmo2 bound to Ldb1(LID) . The ordered regions of Ldb1 in this complex correspond well with binding hotspots previously defined by mutagenic studies. Comparisons of this Lmo2(LIM2) -Ldb1(LID) structure with previously determined structures of the Lmo2/Ldb1(LID) complexes lead to the conclusion that modular binding of tandem LIM domains in Lmo2 to tandem linear motifs in Ldb1 is accompanied by several disorder-to-order transitions and/or conformational changes in both proteins.
LIM 仅蛋白 2(Lmo2)是一种调节蛋白,对造血发育至关重要,T 细胞中 Lmo2 的异常过表达会导致 T 细胞白血病。它通过介导蛋白质-蛋白质相互作用和核多成分转录复合物来发挥作用。Lmo2 通过 Lmo2 的串联 LIM 结构域和 Ldb1 的 LIM 相互作用结构域(LID)与 LIM 域结合蛋白 1(Ldb1)相互作用。在这里,我们展示了 Lmo2(LIM2)与 Ldb1(LID)结合的 LIM2 结构域的溶液结构。该复合物中 Ldb1 的有序区域与先前通过诱变研究定义的结合热点非常吻合。将 Lmo2(LIM2)-Ldb1(LID)结构与先前确定的 Lmo2/Ldb1(LID)复合物结构进行比较,得出结论,串联 LIM 结构域在 Lmo2 中的模块化结合与串联线性基序在 Ldb1 中是伴随着几个无序到有序的转变和/或两个蛋白质的构象变化。