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PDBsum entry 4bxp
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References listed in PDB file
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Key reference
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Title
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Crystal structures of the cpap/stil complex reveal its role in centriole assembly and human microcephaly.
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Authors
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M.A.Cottee,
N.Muschalik,
Y.L.Wong,
C.M.Johnson,
S.Johnson,
A.Andreeva,
K.Oegema,
S.M.Lea,
J.W.Raff,
M.Van breugel.
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Ref.
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Elife, 2013,
2,
e01071.
[DOI no: ]
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PubMed id
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Abstract
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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 CPAP-STIL interaction constitutes a conserved key step in centriole
biogenesis. DOI:http://dx.doi.org/10.7554/eLife.01071.001.
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