7z0f
From Proteopedia
CPAP:S-TUBULIN:IIH5 ALPHAREP COMPLEX
Structural highlights
DiseaseCENPJ_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. FunctionCENPJ_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 PubMedMicrotubule 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. See AlsoReferences
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