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Instruments / Technical Area	Publication Details	Published	Actions
I02-Macromolecular Crystallography I03-Macromolecular Crystallography I04-Macromolecular Crystallography	Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly Matthew Cottee , Nadine Muschalik , Yao Liang Wong , Christopher M Johnson , Steven Johnson , Antonina Andreeva , Karen Oegema , Susan Lea , Jordan W Raff , Mark Van Breugel Elife 2 DOI: 10.7554/eLife.01071 PMID: 24052813 Diamond Proposal Number(s): [8547] Open Access Show Abstract ▼ Abstract: Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel proline recognition domain that forms a 1:1 complex with a short, highly conserved target motif in STIL. Crystal structures of this complex reveal an unusual, all-β structure adopted by the TCP domain and explain how a microcephaly mutation in CPAP compromises complex formation. Through point mutations, we demonstrate that complex formation is essential for centriole duplication in vivo. Our studies provide the first structural insight into how the malfunction of centriole proteins results in human disease and also reveal that the CPAPSTIL interaction constitutes a conserved key step in centriole biogenesis.	Sep 2013

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I02-Macromolecular Crystallography
I03-Macromolecular Crystallography
I04-Macromolecular Crystallography

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

Matthew Cottee , Nadine Muschalik , Yao Liang Wong , Christopher M Johnson , Steven Johnson , Antonina Andreeva , Karen Oegema , Susan Lea , Jordan W Raff , Mark Van Breugel

Elife 2

DOI: 10.7554/eLife.01071

PMID: 24052813

Diamond Proposal Number(s): [8547]