Tubulin tyrosine ligase structure reveals adaptation of an ancient fold to bind and modify tubulin

Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 11/2011; 18(11):1250-8. DOI: 10.1038/nsmb.2148
Source: PubMed


Tubulin tyrosine ligase (TTL) catalyzes the post-translational C-terminal tyrosination of α-tubulin. Tyrosination regulates recruitment of microtubule-interacting proteins. TTL is essential. Its loss causes morphogenic abnormalities and is associated with cancers of poor prognosis. We present the first crystal structure of TTL (from Xenopus tropicalis), defining the structural scaffold upon which the diverse TTL-like family of tubulin-modifying enzymes is built. TTL recognizes tubulin using a bipartite strategy. It engages the tubulin tail through low-affinity, high-specificity interactions, and co-opts what is otherwise a homo-oligomerization interface in structurally related ATP grasp-fold enzymes to form a tight hetero-oligomeric complex with the tubulin body. Small-angle X-ray scattering and functional analyses reveal that TTL forms an elongated complex with the tubulin dimer and prevents its incorporation into microtubules by capping the tubulin longitudinal interface, possibly modulating the partition of tubulin between monomeric and polymeric forms.

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    • "rs peaking / dipping at specific times during TE differentiation ( n = number of proteins in each cluster ) . Dotted gray lines indicate the log 2 - fold thresholds of significant protein accumulation and the red dotted lines represent the appearance of visible TEs as observed in Figure 1A . were also isolated , such as TUBULIN - TYROSINE LIGASE ( Szyk et al . , 2011 ) , casein kinases ( Ben - Nissan et al . , 2008 ) , and histone deacetylases ( Hubbert et al . , 2002 ; Cho and Cavalli , 2012 ) . Other proteins generally recovered in microtubule pull - down experi - ments , and which decorate microtubule structures ( e . g . , the spindle ) , were also found , such as GLYCERALDEHYDE - 3 - PHOSPHATE "
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    The Plant Cell 10/2015; 27(10). DOI:10.1105/tpc.15.00314 · 9.34 Impact Factor
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    • "TTL domains are approximately 350 amino acid modules that catalyze ligation of amino acids to tubulins or other substrates. The TTL domain contains ATP-grasp-like motifs that correspond to the ATP/Mg2+ binding site typical of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity [8]. This domain is present in a family of proteins that has 14 members in mouse. "
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