Structure and dynamics of the homodimeric dynein light chain km23
Structure and dynamics of the homodimeric dynein light chain km23
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DOI：
10.1016/j.jmb.2005.07.002
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发表时间：
2005-09-16
影响因子：
5.6
通讯作者：
Hinck, AP
中科院分区：
文献类型：
--
作者：
Ilangovan, U;Ding, W;Hinck, AP
Km23(96个残基，11 kDa)是果蝇路障的哺乳动物同源基因，是动力蛋白轻链Lc7/Rob1/km23类的创始成员。KM23在转化生长因子β受体激活后被丝氨酸磷酸化，并在这种磷酸化反应中结合动力蛋白中间链。在这里，我们报道了km23的三维溶液结构，它是一种同源二聚体，类似于MglB/Robl超家族的两个远亲成员p14和MP1之间形成的异二聚体复合体，但不同于Lc8和Tctex-1类动力蛋白轻链，后者也采用同源二聚体结构。Km23的保守表面残基，包括3个丝氨酸残基，主要位于分子的单一表面。与这一面相邻的是由相反单体的环不完全重叠形成的大裂缝。根据在两个场收集的核磁共振弛豫数据，几个裂隙残基在ns-PS和ms-Mu S的时间尺度上是灵活的。基于这些观察，我们认为分子中央面上的保守残基斑块对应于km23与动力蛋白中间链结合的位置，而在两个单体的环重叠之间形成的柔性裂缝对应于km23与其他伙伴结合的位置，如转化生长因子II型受体或Smad2。(C)2005爱思唯尔有限公司。保留所有权利。
km23 (96 residues, 11 kDa) is the mammalian ortholog of Drosophila roadblock, the founding member of LC7/robl/km23 class of dynein light chains. km23 has been shown to be serine-phosphorylated following TGF beta receptor activation and to bind the dynein intermediate chain in response to such phosphorylation. Here, we report the three-dimensional solution structure of km23, which is shown to be that of a homodimer, similar to that observed for the heterodimeric complex formed between p14 and MP1, two distantly related members of the MglB/robl superfamily, but distinct from the LC8 and Tctex-1 classes of dynein light chains, which also adopt homodimeric structures. The conserved surface residues of km23, including three serine residues, are located predominantly on a single face of the molecule. Adjacent to this face is a large cleft formed by the incomplete overlap of loops from opposite monomers. As shown by NMR relaxation data collected at two fields, several cleft residues are flexible on the ns-ps and ms-mu s timescales. Based on these observations, we propose that the patch of conserved residues on the central face of the molecule corresponds to the site at which km23 binds the dynein intermediate chain and that the flexible cleft formed between the overlap of loops from the two monomers corresponds to the site at which km23 binds other partners, such as the TGF type II receptor or Smad2. (c) 2005 Elsevier Ltd. All rights reserved.