Structural Basis of Formation of the Microtubule Minus-End-Regulating CAMSAP-Katanin Complex
Structural Basis of Formation of the Microtubule Minus-End-Regulating CAMSAP-Katanin Complex
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DOI：
10.1016/j.str.2017.12.017
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发表时间：
2018-03-06
期刊：
影响因子：
5.7
通讯作者：
Akhmanova, Anna
中科院分区：
文献类型：
--
作者：
Jiang, Kai;Faltova, Lenka;Akhmanova, Anna
CAMSAP/Patronin家族成员在从有丝分裂纺锤体到分化的上皮细胞和神经元的各种系统中调节微管负末端的组织和稳定性。哺乳动物CAMSAP 2和CAMSAP 3与生长中的微管负末端结合，在那里它们形成稳定的微管晶格的延伸。微管保护ATP酶katanin与CAMSAP相互作用并限制CAMSAP修饰的微管延伸的长度。在这里，通过使用生物化学，生物物理学和结构的方法，我们揭示了CAMSAP 2和CAMSAP 3中保守的短螺旋基序分别与katanin亚基p60和p80的N-和C-末端结构域形成的异二聚体结合。所鉴定的CAMSAP-katanin结合模式得到突变分析和基因组编辑实验的支持。它与ASPM-katanin复合物中所见的非常相似，后者负责有丝分裂纺锤体中微管负端的调节。我们的工作为katanin与主要微管负端调节剂的合作提供了一般的分子机制。
CAMSAP/Patronin family members regulate the organization and stability of microtubule minus ends in various systems ranging from mitotic spindles to differentiated epithelial cells and neurons. Mammalian CAMSAP2 and CAMSAP3 bind to growing microtubule minus ends, where they form stretches of stabilized microtubule lattice. The microtubulesevering ATPase katanin interacts with CAMSAPs and limits the length of CAMSAP-decorated microtubule stretches. Here, by using biochemical, biophysical, and structural approaches, we reveal that a short helical motif conserved in CAMSAP2 and CAMSAP3 binds to the heterodimer formed by the N- and C-terminal domains of katanin subunits p60 and p80, respectively. The identified CAMSAP-katanin binding mode is supported by mutational analysis and genome-editing experiments. It is strikingly similar to the one seen in the ASPM-katanin complex, which is responsible for microtubule minus-end regulation in mitotic spindles. Our work provides a general molecular mechanism for the cooperation of katanin with major microtubule minus-end regulators.