Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly

• DOI: 10.7554/elife.01071
• Publication Date: 2013-09-17T15:40:27Z
• Authors: Matthew A Cottee; Nadine Muschalik; Yao Liang Wong; Christopher M Joh...; Steven Johnson; Antonina Andreeva; Karen Oegema; Susan M Lea; Jordan W Raff; Mark van Breugel
• Keywords: Centriole; Microcephaly; Ciliogenesis; Basal body

Centrioles organise centrosomes and template cilia flagella. Several centriole centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) STIL (MCPH7) are required for assembly, but it is unclear how mutations in them lead microcephaly. We show that the TCP domain of constitutes novel proline recognition forms 1:1 complex short, highly conserved target motif STIL. Crystal structures this reveal an unusual, all-β structure adopted by explain mutation compromises formation. Through point mutations, we demonstrate formation essential duplication vivo. Our studies provide first structural insight into malfunction results human also CPAP–STIL interaction key step biogenesis.