Jin Xiangshu, Touhey Jason, Gaudet Rachelle
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
J Biol Chem. 2006 Sep 1;281(35):25006-10. doi: 10.1074/jbc.C600153200. Epub 2006 Jun 29.
The TRPV ion channels mediate responses to many sensory stimuli including heat, low pH, neuropeptides, and chemical ligands. All TRPV subfamily members contain an intracellular N-terminal ankyrin repeat domain (ARD), a prevalent protein interaction motif. The 1.6-A crystal structure of the TRPV2-ARD, with six ankyrin repeats, reveals several atypical structural features. Repeats one through three display unusually long and flexible fingers with a large number of exposed aromatic residues, whereas repeats five and six have unusually long outer helices. Furthermore, a large counterclockwise twist observed in the stacking of repeats four and five breaks the regularity of the domain, altering the shape of surfaces available for interactions with proteins or other cellular ligands. Both solution studies and crystal packing interactions indicate that the TRPV2-ARD does not form homo-oligomers, suggesting that the ARD of TRPV ion channels may be used for interactions with regulatory factors rather than in promoting tetrameric assembly of the ion channels.
瞬时受体电位香草酸亚家族（TRPV）离子通道介导对多种感觉刺激的反应，包括热、低pH值、神经肽和化学配体。所有TRPV亚家族成员都包含一个细胞内N端锚蛋白重复结构域（ARD），这是一种普遍存在的蛋白质相互作用基序。具有六个锚蛋白重复序列的TRPV2-ARD的1.6埃晶体结构揭示了几个非典型的结构特征。第一到第三个重复序列显示出异常长且灵活的指状结构，带有大量暴露的芳香族残基，而第五和第六个重复序列具有异常长的外部螺旋。此外，在第四个和第五个重复序列的堆积中观察到一个大的逆时针扭转，打破了结构域的规则性，改变了可用于与蛋白质或其他细胞配体相互作用的表面形状。溶液研究和晶体堆积相互作用均表明，TRPV2-ARD不会形成同型寡聚体，这表明TRPV离子通道的ARD可能用于与调节因子相互作用，而不是促进离子通道的四聚体组装。
