Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture.
Bottom Line: Centrioles are evolutionarily conserved eukaryotic organelles composed of a protein scaffold surrounded by sets of microtubules organized with a 9-fold radial symmetry.The G-box comprises a single elongated β sheet capable of forming supramolecular assemblies.Structural and biophysical studies highlight the conserved nature of the CPAP-STIL complex.
Affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.Show MeSH
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Mentions: A previous cryo-tomographic study of purified C. reinhardtii basal bodies showed distinct electron densities in the vicinity of the microtubule wall (Li et al., 2012). We propose that CPAP accounts for an elongated density observed there that lies roughly parallel to the microtubule triplet (Figures 4A and 4B). The CPAP C terminus, which interacts with Cep135 (Lin et al., 2013), would be placed close to the A-tubule as part of the overall “pinhead” assembly that connects cartwheels to microtubules, and where Cep135/Bld10p also locates (Hiraki et al., 2007). The 24-nm-long CPAP coiled coil would then stretch approximately to the beginning of the C-tubule, where the CPAP N terminus could form connections through its microtubule associating segments (Hsu et al., 2008). Thus, we propose that CPAP acts as a horizontal “strut,” linking the pinhead with microtubules and reinforcing the overall centriole assembly. It is possible that differences in CPAP length among organisms are related to apparent differences in microtubule tilt with respect to cartwheel spokes; however, further modeling efforts would be required to assess this hypothesis.
Affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.