Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.
Recognition of C-terminal amino acids in tubulin by pore loops in Spastin is important for microtubule severing.
复制标题
通过孔隙环在微管蛋白中识别小管中的C末端氨基酸对于微管切断很重要。
DOI：
10.1083/jcb.200610072
复制
发表时间：
2007-03-26
影响因子：
7.8
通讯作者：
Lauring, Brett
中科院分区：
文献类型：
--
作者：
White, Susan Roehl;Evans, Katia J;Lary, Jeffrey;Cole, James L;Lauring, Brett
Spastin是一种在遗传性痉挛截瘫的神经退行性疾病中突变的AAA-ATPase，它切断了微管。许多其他AAA蛋白形成环状六角体，并含有孔环，这些孔环伸入环的中央空腔，充当棘轮，拉动目标蛋白，在某些情况下，导致构象变化。我们发现Spastin组装成一个六角体，在中心孔内的环识别微管蛋白的C-端氨基酸。关键的孔环氨基酸是切断所必需的，包括一种被疾病相关突变改变的氨基酸。我们还发现Spastin含有第二个微管结合域，它与微管发生明显的相互作用，是切断微管所必需的。考虑到Spastin在两个位置与MT结合，并且这两种相互作用都是需要切断的，我们认为切断是通过施加在微管蛋白C-末端的力来发生的，这导致微管蛋白的构象变化，从而将其从聚合物中释放出来。
Spastin, an AAA ATPase mutated in the neurodegenerative disease hereditary spastic paraplegia, severs microtubules. Many other AAA proteins form ring-shaped hexamers and contain pore loops, which project into the ring's central cavity and act as ratchets that pull on target proteins, leading, in some cases, to conformational changes. We show that Spastin assembles into a hexamer and that loops within the central pore recognize C-terminal amino acids of tubulin. Key pore loop amino acids are required for severing, including one altered by a disease-associated mutation. We also show that Spastin contains a second microtubule binding domain that makes a distinct interaction with microtubules and is required for severing. Given that Spastin engages the MT in two places and that both interactions are required for severing, we propose that severing occurs by forces exerted on the C-terminal tail of tubulin, which results in a conformational change in tubulin, which releases it from the polymer.