7q1e

CPAP:TUBULIN:IIH5 ALPHAREP COMPLEXCPAP:TUBULIN:IIH5 ALPHAREP COMPLEX

Structural highlights

7q1e is a 5 chain structure with sequence from Homo sapiens, Ovis aries and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CENPJ_HUMAN Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

CENPJ_HUMAN Plays an important role in cell division and centrosome function by participating in centriole duplication. Inhibits microtubule nucleation from the centrosome.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Microtubule dynamics is regulated by various cellular proteins and perturbed by small-molecule compounds. To what extent the mechanism of the former resembles that of the latter is an open question. We report here structures of tubulin bound to the PN2-3 domain of CPAP, a protein controlling the length of the centrioles. We show that an alpha-helix of the PN2-3 N-terminal region binds and caps the longitudinal surface of the tubulin beta subunit. Moreover, a PN2-3 N-terminal stretch lies in a beta-tubulin site also targeted by fungal and bacterial peptide-like inhibitors of the vinca domain, sharing a very similar binding mode with these compounds. Therefore, our results identify several characteristic features of cellular partners that bind to this site and highlight a structural convergence of CPAP with small-molecule inhibitors of microtubule assembly.

Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors.,Campanacci V, Urvoas A, Ammar Khodja L, Aumont-Nicaise M, Noiray M, Lachkar S, Curmi PA, Minard P, Gigant B Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2120098119. doi: , 10.1073/pnas.2120098119. Epub 2022 May 4. PMID:35507869^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hung LY, Chen HL, Chang CW, Li BR, Tang TK. Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. Mol Biol Cell. 2004 Jun;15(6):2697-706. Epub 2004 Mar 26. PMID:15047868 doi:http://dx.doi.org/10.1091/mbc.E04-02-0121
↑ Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002
↑ Chang J, Cizmecioglu O, Hoffmann I, Rhee K. PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 2010 Jul 21;29(14):2395-406. doi: 10.1038/emboj.2010.118. Epub 2010 Jun, 8. PMID:20531387 doi:10.1038/emboj.2010.118
↑ Campanacci V, Urvoas A, Ammar Khodja L, Aumont-Nicaise M, Noiray M, Lachkar S, Curmi PA, Minard P, Gigant B. Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors. Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2120098119. PMID:35507869 doi:10.1073/pnas.2120098119

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OCA

[1] Hung LY, Chen HL, Chang CW, Li BR, Tang TK. Identification of a novel microtubule-destabilizing motif in CPAP that binds to tubulin heterodimers and inhibits microtubule assembly. Mol Biol Cell. 2004 Jun;15(6):2697-706. Epub 2004 Mar 26. PMID:15047868 doi:http://dx.doi.org/10.1091/mbc.E04-02-0121

[2] Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002

[3] Chang J, Cizmecioglu O, Hoffmann I, Rhee K. PLK2 phosphorylation is critical for CPAP function in procentriole formation during the centrosome cycle. EMBO J. 2010 Jul 21;29(14):2395-406. doi: 10.1038/emboj.2010.118. Epub 2010 Jun, 8. PMID:20531387 doi:10.1038/emboj.2010.118

[4] Campanacci V, Urvoas A, Ammar Khodja L, Aumont-Nicaise M, Noiray M, Lachkar S, Curmi PA, Minard P, Gigant B. Structural convergence for tubulin binding of CPAP and vinca domain microtubule inhibitors. Proc Natl Acad Sci U S A. 2022 May 10;119(19):e2120098119. PMID:35507869 doi:10.1073/pnas.2120098119

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