Abstract
The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. The centrosome is a membraneless organelle composed of two microtubule-derived structures called centrioles and an amorphous mass of pericentriolar material. Super-resolution microscopic analyses in various organisms revealed that diverse pericentriolar material proteins are concentrically localized around a centriole in a highly organized manner. However, the molecular nature underlying these organizations remains unknown. Here we show that two human pericentriolar material scaffolds, Cep63 and Cep152, cooperatively generate a heterotetrameric α-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk4, a key regulator for centriole duplication. Mutations disrupting the self-assembly abrogate Plk4-mediated centriole duplication. Because pericentriolar material organization is evolutionarily conserved, this work may offer a paradigm for investigating the assembly and function of centrosomal scaffolds in various organisms.
Highlights
The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents
The centrosome, which plays a central role as the main microtubule (MT)-organizing center for animal cell division, is a membraneless organelle composed of a pair of orthogonally arranged MT-derived apparatus, called centrioles, and the surrounding pericentriolar material (PCM)1,2
Since Cep152 is thought to function as a licensing factor for Plk4-mediated centriole biogenesis19, investigating the mechanism of how Cep152 functions in conjunction with Cep63 to self-assemble a macroscale structural entity will be important to comprehend the centrosomal architecture critically required for Plk4-dependent centriole duplication
Summary
The cell is constructed by higher-order structures and organelles through complex interactions among distinct structural constituents. We show that two human pericentriolar material scaffolds, Cep and Cep152, cooperatively generate a heterotetrameric α-helical bundle that functions in conjunction with its neighboring hydrophobic motifs to self-assemble into a higher-order cylindrical architecture capable of recruiting downstream components, including Plk, a key regulator for centriole duplication. Aberrations in the function of PCM scaffolds are associated with many human diseases, including cancer, microcephaly, ciliopathy, and dwarfism7,8 At present, how this membraneless cellular architecture is assembled and how the centrosomal scaffold proteins display a cylindrical pattern of localization around a centriole remain unknown. We demonstrate that two of the human PCM scaffolds, Cep and Cep15212–14, cooperate to generate a higher-order cylindrical self-assembly capable of recruiting their downstream components, such as Plk, a key regulator of centriole duplication. Since Cep152 is thought to function as a licensing factor for Plk4-mediated centriole biogenesis, investigating the mechanism of how Cep152 functions in conjunction with Cep to self-assemble a macroscale structural entity will be important to comprehend the centrosomal architecture critically required for Plk4-dependent centriole duplication
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