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A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences

In cells, 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 conserve...

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Autores principales: Lindsay, K. Alice, Abdelhamid, Nedine, Kahawatte, Shehani, Dima, Ruxandra I., Sackett, Dan L., Finegan, Tara M., Ross, Jennifer L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136189/
https://www.ncbi.nlm.nih.gov/pubmed/37189368
http://dx.doi.org/10.3390/biom13040620
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author Lindsay, K. Alice
Abdelhamid, Nedine
Kahawatte, Shehani
Dima, Ruxandra I.
Sackett, Dan L.
Finegan, Tara M.
Ross, Jennifer L.
author_facet Lindsay, K. Alice
Abdelhamid, Nedine
Kahawatte, Shehani
Dima, Ruxandra I.
Sackett, Dan L.
Finegan, Tara M.
Ross, Jennifer L.
author_sort Lindsay, K. Alice
collection PubMed
description In cells, 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 the 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 CTT 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.
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spelling pubmed-101361892023-04-28 A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences Lindsay, K. Alice Abdelhamid, Nedine Kahawatte, Shehani Dima, Ruxandra I. Sackett, Dan L. Finegan, Tara M. Ross, Jennifer L. Biomolecules Article In cells, 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 the 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 CTT 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. MDPI 2023-03-30 /pmc/articles/PMC10136189/ /pubmed/37189368 http://dx.doi.org/10.3390/biom13040620 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lindsay, K. Alice
Abdelhamid, Nedine
Kahawatte, Shehani
Dima, Ruxandra I.
Sackett, Dan L.
Finegan, Tara M.
Ross, Jennifer L.
A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title_full A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title_fullStr A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title_full_unstemmed A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title_short A Tale of 12 Tails: Katanin Severing Activity Affected by Carboxy-Terminal Tail Sequences
title_sort tale of 12 tails: katanin severing activity affected by carboxy-terminal tail sequences
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136189/
https://www.ncbi.nlm.nih.gov/pubmed/37189368
http://dx.doi.org/10.3390/biom13040620
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