Lindsay, K.A.; Abdelhamid, N.; Kahawatte, S.; Dima, R.I.; Sackett, D.L.; Finegan, T.M.; Ross, J.L. A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences. Biomolecules2023, 13, 620.
Lindsay, K.A.; Abdelhamid, N.; Kahawatte, S.; Dima, R.I.; Sackett, D.L.; Finegan, T.M.; Ross, J.L. A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences. Biomolecules 2023, 13, 620.
Lindsay, K.A.; Abdelhamid, N.; Kahawatte, S.; Dima, R.I.; Sackett, D.L.; Finegan, T.M.; Ross, J.L. A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences. Biomolecules2023, 13, 620.
Lindsay, K.A.; Abdelhamid, N.; Kahawatte, S.; Dima, R.I.; Sackett, D.L.; Finegan, T.M.; Ross, J.L. A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences. Biomolecules 2023, 13, 620.
Abstract
In celIs, microtubule location, length, and dynamics are regulated by a host of microtubule-associated proteins and enzymes that read where to bind and act based on the microtubule “tubulin code,” which is predominantly encoded in the tubulin carboxy-terminal tail (CTT). Katanin is a highly conserved AAA ATPase enzyme that binds to the tubulin CTTs to remove dimers and sever microtubules. We have previously demonstrated that short CTT peptides are able to inhibit katanin severing. Here, we examine effects of CTT sequences on this inhibition activity. Specifically, we examine CTT sequences found in nature, alpha1A (TUBA1A), detyrosinated alpha1A, Δ2 alpha1A, beta5 (TUBB/TUBB5), beta2a (TUBB2A), beta3 (TUBB3), and beta4b (TUBB4b). We find that these natural CTTs have distinct abilities to inhibit, most noticeably beta3 cannot inhibit katanin. Two non-native CTT tail constructs are also unable to inhibit – despite having 94% sequence identity with alpha1 or beta5 sequences. Surprisingly, we demonstrate that poly-E and poly-D peptides are capable of inhibiting katanin significantly. An analysis of the hydrophobicity of the CTT constructs indicates that more hydrophobic polypeptides are less inhibitory than more polar polypeptides. These experiments not only demonstrate inhibition, but also likely interaction and targeting of katanin to these various CTTs when they are part of a polymerized microtubule filament.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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