Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding modules named NWE, SNYG, and ELLEn, and PYG and GFG-repeat by their signature motifs. These modules intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The modules molecular characteristics provided keys to identify elusive cross-species homologs, hitherto unknown human MIP candidates, and functional properties for seven protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work defines structural innovations that underpin centriole and axoneme assembly and demonstrates that MIPs co-evolved with centrosomes and cilia.

中心体和纤毛是基于微管的上层结构，对于细胞分裂、信号传导和运动至关重要。曾经被认为是微管核心结构的中空管腔最近被发现含有丰富的微管内部蛋白（MIP）网状结构。为了解决不同的 MIP 如何进化来识别微管内表面这一突出问题，我们应用计算序列分析、结构预测和实验验证来揭示进化上保守的微管和 MIP 结合模块，名为 NWE、SNYG 和 ELLEn、PYG 和GFG-重复他们的标志性图案。这些模块与 24 种衣藻和 33 种人类蛋白质中的 MT 结合 DM10 模块和 Mn 重复序列混合。这些模块的分子特征为识别难以捉摸的跨物种同源物、迄今为止未知的人类 MIP 候选物以及七个蛋白质亚家族（包括微管接缝结合 NWE 和 ELLEn 家族）的功能特性提供了关键。我们的工作定义了支撑中心粒和轴丝组装的结构创新，并证明 MIP 与中心体和纤毛共同进化。