Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom.
Sci Rep. 2012;2:695. doi: 10.1038/srep00695. Epub 2012 Sep 26.
The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases.
ROCO 蛋白家族是一大类具有多种结构域的蛋白，其特征是存在 Ras 相关蛋白（ROC）结构域，其后是 COR 或 C 端 ROC 结构域。先前已经表明，人类 ROCO 蛋白 Leucine Rich Repeat Kinase 2（LRRK2）的 ROC 结构域控制其激酶活性。在这里，评估了另一种人类 ROCO 蛋白 Death Associated Protein Kinase 1（DAPK1）的 ROC 结构域结合 GTP 和控制其激酶活性的能力。与 LRRK2 不同，DAPK1 失去 GTP 结合不会导致激酶活性丧失，而是调节这种活性。这些数据突出了 DAPK1 的 ROC 结构域作为该蛋白功能调节剂的靶标，并揭示了 ROC 结构域作为具有广泛人类疾病意义的复杂蛋白中分子内调节剂的作用。
