Molecular architecture of the augmin complex.

Molecular architecture of the augmin complex.
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DOI:
10.1038/s41467-022-33227-7
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发表时间:
2022-09-16
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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有丝分裂过程中染色体的准确分离取决于有丝分裂纺锤体的正确组装,有丝分裂纺锤体是一种主要由微管组成的双极性结构。augmin复合体,或与augmin亚单位(HAUS)复合体同源,是一种8个亚单位的蛋白质复合体,需要在后生动物中构建强健的有丝分裂纺锤体。Augmin通过招募γ-微管蛋白环复合物(γ-TuRC)到先前存在的微管和成核分支微管中来增加纺锤体内的微管密度。在这里,我们通过单粒子冷冻电子显微镜(cryo-EM)、计算方法和交联质谱(CLMS)来阐明augmin的分子结构。Augmin的高度灵活的结构包含一个v形头部和一个丝状尾部,头部存在扩展或收缩构象状态。我们的工作强调了冷冻电镜,辅以计算进步和CLMS,如何阐明具有挑战性的蛋白质复合物的结构,并提供了对augmin在介导微管分支成核中的功能的见解。在细胞分裂过程中,8个亚单位的增蛋白复合体是分支微管成核和产生强大的有丝分裂纺锤体所必需的。在这里,作者使用低温电镜,交联质谱和计算工具来建立人类augmin复合物的结构模型。
Accurate segregation of chromosomes during mitosis depends on the correct assembly of the mitotic spindle, a bipolar structure composed mainly of microtubules. The augmin complex, or homologous to augmin subunits (HAUS) complex, is an eight-subunit protein complex required for building robust mitotic spindles in metazoa. Augmin increases microtubule density within the spindle by recruiting the γ-tubulin ring complex (γ-TuRC) to pre-existing microtubules and nucleating branching microtubules. Here, we elucidate the molecular architecture of augmin by single particle cryo-electron microscopy (cryo-EM), computational methods, and crosslinking mass spectrometry (CLMS). Augmin’s highly flexible structure contains a V-shaped head and a filamentous tail, with the head existing in either extended or contracted conformational states. Our work highlights how cryo-EM, complemented by computational advances and CLMS, can elucidate the structure of a challenging protein complex and provides insights into the function of augmin in mediating microtubule branching nucleation. The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.
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