PDBsum entry 4bxr

Cell cycle

PDB id: 4bxr

Contents

Protein chains

183 a.a.

12 a.a.

14 a.a.

Waters ×54

PDB id:

4bxr

Name:

Cell cycle

Title:

Structure of the wild-type tcp10 domain of danio rerio cpap in complex with a peptide of danio rerio stil

Structure:

Cpap. Chain: a, b. Fragment: tcp-10 domain, residues 937-1124. Engineered: yes. Scl-interrupting locus protein homolog. Chain: c, d. Fragment: stil peptide, residues 408-428. Engineered: yes

Source:

Danio rerio. Zebrafish. Organism_taxid: 7955. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta. Expression_system_variant: c41

Resolution:

2.20Å R-factor: 0.236 R-free: 0.277

Authors:

M.Van Breugel

Key ref:

M.A.Cottee et al. (2013). Crystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly. Elife, 2, e01071. PubMed id: 24052813 DOI: 10.7554/eLife.01071

Date:

15-Jul-13 Release date: 25-Sep-13

Protein chains

E7FCY1  (E7FCY1_DANRE) -  Centromere protein J from Danio rerio

Seq: 1124 a.a.

Struc: 183 a.a.

Protein chain

Q8JGS1  (STIL_DANRE) -  SCL-interrupting locus protein homolog from Danio rerio

Seq: 1263 a.a.

Struc: 12 a.a.

Protein chain

Q8JGS1  (STIL_DANRE) -  SCL-interrupting locus protein homolog from Danio rerio

Seq: 1263 a.a.

Struc: 14 a.a.

DOI no: 10.7554/eLife.01071

Elife 2:e01071 (2013)

PubMed id: 24052813

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

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.

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 CPAP-STIL interaction constitutes a conserved key step in centriole biogenesis. DOI:http://dx.doi.org/10.7554/eLife.01071.001.