PUBLICATION
Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture
- Authors
- Hatzopoulos, G.N., Erat, M.C., Cutts, E., Rogala, K.B., Slater, L.M., Stansfeld, P.J., Vakonakis, I.
- ID
- ZDB-PUB-200522-23
- Date
- 2013
- Source
- Structure (London, England : 1993) 21: 2069-77 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Cycle Proteins
- Centrioles/chemistry*
- Crystallography, X-Ray
- Humans
- Microcephaly/genetics
- Microtubule-Associated Proteins/chemistry*
- Microtubule-Associated Proteins/genetics
- Models, Molecular
- Mutation, Missense
- Protein Binding
- Protein Structure, Secondary
- Protein Structure, Tertiary
- Zebrafish*
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- PubMed
- 24076405 Full text @ Structure
Citation
Hatzopoulos, G.N., Erat, M.C., Cutts, E., Rogala, K.B., Slater, L.M., Stansfeld, P.J., Vakonakis, I. (2013) Structural analysis of the G-box domain of the microcephaly protein CPAP suggests a role in centriole architecture. Structure (London, England : 1993). 21:2069-77.
Abstract
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.
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