Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding.
Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding.
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DOI：
10.1016/j.str.2021.01.001
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发表时间：
2021-06-03
期刊：
影响因子：
--
通讯作者：
Trempe JF
中科院分区：
文献类型：
--
作者：
Khan N;Pelletier D;McAlear TS;Croteau N;Veyron S;Bayne AN;Black C;Ichikawa M;Khalifa AAZ;Chaaban S;Kurinov I;Brouhard G;Bechstedt S;Bui KH;Trempe JF
Parkin共调节基因(PACRG)结合在轴丝的双微管之间的内部连接处，这种结构存在于鞭毛和纤毛中。PACRG与适配器蛋白减数分裂表达基因1(MEIG1)结合，但它们如何与微管结合尚不清楚。在这里，我们报道了人PACRG与MEIG1的络合物的晶体结构。PACRG采用带有与MEIG1相互作用的环的螺旋重复折叠。利用原生动物莱茵衣藻的轴丝二联微管的结构和单分子荧光显微镜，我们认为PACRG与微管结合，同时招募游离微管蛋白来催化内连接的形成。我们发现，同源的PACRG样蛋白也介导了双重的微管蛋白相互作用，但不与MEIG1结合。我们的发现建立了一个框架，以评估PACRG蛋白家族和MEIG1在调节轴丝组装中的功能。可汗等人。解决了人类PACRG的晶体结构：MEIG1，一种对精子鞭毛成熟至关重要的蛋白质复合体。PACRG和其同系物PACRGL可以通过多个结合位点将微管蛋白招募到微管中，这可能是鞭毛和纤毛中发现的轴丝双线微管的形成机制。
The Parkin Co-Regulated Gene (PACRG) binds at the inner junction between doublet microtubules of the axoneme, a structure found in flagella and cilia. PACRG binds to the adaptor protein meiosis expressed gene 1 (MEIG1), but how they bind to microtubules is unknown. Here, we report the crystal structure of human PACRG in complex with MEIG1. PACRG adopts a helical repeat fold with a loop that interacts with MEIG1. Using the structure of the axonemal doublet microtubule from the protozoan Chlamydomonas reinhardtii and single-molecule fluorescence microscopy, we propose that PACRG binds to microtubules while simultaneously recruiting free tubulin to catalyze formation of the inner junction. We show that the homologous PACRG-like protein also mediates dual tubulin interactions but does not bind MEIG1. Our findings establish a framework to assess the function of the PACRG family of proteins and MEIG1 in regulating axoneme assembly. Khan et al. solved the crystal structure of human PACRG:MEIG1, a protein complex essential for flagella maturation in sperm. PACRG and its homolog PACRGL can recruit tubulin to microtubules via multiple binding sites, suggesting a mechanism for formation of the axonemal doublet microtubule found in flagella and cilia.
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影响因子：
4.8
作者：
Goldberg, MS;Fleming, SM;Shen, J
通讯作者：
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DOI：
10.1073/pnas.1901805116
发表时间：
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影响因子：
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