Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture.
Georgios N Hatzopoulos, Michèle C Erat, Erin Cutts, Kacper B Rogala, Leanne M Slater, Philip J Stansfeld, Ioannis Vakonakis@.
Structure. 21(11):2069-77. 2013 November 5.
blue & bold — Rogala Lab member
Ψ — equal contribution
@ — corresponding author
Centrioles are evolutionarily conserved eukaryotic organelles composed of a protein scaffold surrounded by sets of microtubules organized with a 9-fold radial symmetry. CPAP, a centriolar protein essential for microtubule recruitment, features a C-terminal domain of unknown structure, the G-box. A missense mutation in the G-box reduces affinity for the centriolar shuttling protein STIL and causes primary microcephaly. Here, we characterize the molecular architecture of CPAP and determine the G-box structure alone and in complex with a STIL fragment. 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. We propose that CPAP acts as a horizontal “strut” that joins the centriolar scaffold with microtubules, whereas G-box domains form perpendicular connections.