5itz | pdb_00005itz
Crystal structure of the SAC domain of CPAP in a complex with Tubulin and Darpin
Structural highlights
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[TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [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] [TBB2B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). Publication Abstract from PubMedCentrioles are fundamental and evolutionarily conserved microtubule-based organelles whose assembly is characterized by microtubule growth rates that are orders of magnitude slower than those of cytoplasmic microtubules. Several centriolar proteins can interact with tubulin or microtubules, but how they ensure the exceptionally slow growth of centriolar microtubules has remained mysterious. Here, we bring together crystallographic, biophysical, and reconstitution assays to demonstrate that the human centriolar protein CPAP (SAS-4 in worms and flies) binds and "caps" microtubule plus ends by associating with a site of beta-tubulin engaged in longitudinal tubulin-tubulin interactions. Strikingly, we uncover that CPAP activity dampens microtubule growth and stabilizes microtubules by inhibiting catastrophes and promoting rescues. We further establish that the capping function of CPAP is important to limit growth of centriolar microtubules in cells. Our results suggest that CPAP acts as a molecular lid that ensures slow assembly of centriolar microtubules and, thereby, contributes to organelle length control. Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth.,Sharma A, Aher A, Dynes NJ, Frey D, Katrukha EA, Jaussi R, Grigoriev I, Croisier M, Kammerer RA, Akhmanova A, Gonczy P, Steinmetz MO Dev Cell. 2016 May 23;37(4):362-76. doi: 10.1016/j.devcel.2016.04.024. PMID:27219064[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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