Kizawa Kenji, Jinbo Yuji, Inoue Takafumi, Takahara Hidenari, Unno Masaki, Heizmann Claus W, Izumi Yoshinobu
Innovative Beauty Science Laboratory, Kanebo Cosmetics Inc., Odawara, Japan.
Biochim Biophys Acta. 2013 Jul;1833(7):1712-9. doi: 10.1016/j.bbamcr.2012.07.009. Epub 2012 Jul 28.
The S100A3 homotetramer assembles upon citrullination of a specific symmetric Arg51 pair on its homodimer interface in human hair cuticular cells. Each S100A3 subunit contains two EF-hand-type Ca(2+)-binding motifs and one (Cys)3His-type Zn(2+)-binding site in the C-terminus. The C-terminal coiled domain is cross-linked to the presumed docking surface of the dimeric S100A3 via a disulfide bridge. The aim of this study was to determine the structural and functional role of the C-terminal Zn(2+)-binding domain, which is unique to S100A3, in homotetramer assembly. The binding of either Ca(2+) or Zn(2+) reduced the α-helix content of S100A3 and modulated its affinity for the other cation. The binding of a single Zn(2+) accelerated the Ca(2+)-dependent tetramerization of S100A3 while inducing an extensive unfolding of helix IV. The Ca(2+) and Zn(2+) binding affinities of S100A3 were enhanced when the other cation bound in concert with the tetramerization of S100A3. Small angle scattering analyses revealed that the overall structure of the S100A3 tetramer bound both Ca(2+) and Zn(2+) had a similar molecular shape to the Ca(2+)-bound form in solution. The binding states of the Ca(2+) or Zn(2+) to each S100A3 subunit within a homotetramer appear to be propagated by sensing the repositioning of helix III and the rearrangement of the C-terminal tail domain. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
在人毛发角质形成细胞中，S100A3同四聚体在其二聚体界面上特定的对称精氨酸51对发生瓜氨酸化时组装而成。每个S100A3亚基在C端含有两个EF手型Ca(2+)结合基序和一个(Cys)3His型Zn(2+)结合位点。C端卷曲结构域通过二硫键与二聚体S100A3的假定对接表面交联。本研究的目的是确定S100A3特有的C端Zn(2+)结合结构域在同四聚体组装中的结构和功能作用。Ca(2+)或Zn(2+)的结合降低了S100A3的α螺旋含量，并调节了其对另一种阳离子的亲和力。单个Zn(2+)的结合加速了S100A3的Ca(2+)依赖性四聚化，同时诱导螺旋IV的广泛展开。当另一种阳离子与S10A3的四聚化协同结合时，S100A3的Ca(2+)和Zn(2+)结合亲和力增强。小角散射分析表明，结合了Ca(2+)和Zn(2+)的S100A3四聚体的整体结构在溶液中与结合Ca(2+)的形式具有相似的分子形状。同四聚体内每个S100A3亚基上Ca(2+)或Zn(2+)的结合状态似乎是通过感知螺旋III的重新定位和C端尾部结构域的重排而传播的。本文是名为“第12届欧洲钙研讨会”的特刊的一部分。
