与疾病相关的 p150(Glued)亚基突变使 CAP-gly 结构域不稳定。
Disease-associated mutations in the p150(Glued) subunit destabilize the CAP-gly domain.
机构信息
Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, California 91010, USA.
出版信息
Biochemistry. 2010 Jun 29;49(25):5083-5. doi: 10.1021/bi100235z.
Abstract
Point mutations within the CAP-gly domain of the p150(Glued) subunit of the dynactin complex have been identified in patients with distal spinal bulbar muscular atrophy (dSBMA) and Perry's syndrome. Herein, we show by CD and NMR experiments that each mutated CAP-gly domain is folded but less stable than the wild-type (WT) domain. We also demonstrate that the domains harboring these mutations bind to microtubules but fail to bind to EB1. These data indicate that these disease-associated, point mutations affect the stability of this domain and inhibit their interaction with EB1 but do not inhibit their interaction with microtubules.
摘要
动力蛋白激活蛋白复合体 p150(Glued)亚基的 CAP-gly 结构域内的点突变已在远端脊髓延髓肌肉萎缩症（dSBMA）和佩里综合征患者中被发现。在此，我们通过 CD 和 NMR 实验表明，每个突变的 CAP-gly 结构域都是折叠的，但不如野生型（WT）结构域稳定。我们还证明，这些突变体结构域可以与微管结合，但不能与 EB1 结合。这些数据表明，这些与疾病相关的点突变会影响该结构域的稳定性并抑制其与 EB1 的相互作用，但不抑制其与微管的相互作用。
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