Structural basis of tubulin tyrosination by tubulin tyrosine ligase

Author:

Prota Andrea E.1,Magiera Maria M.2,Kuijpers Marijn3,Bargsten Katja1,Frey Daniel1,Wieser Mara1,Jaussi Rolf1,Hoogenraad Casper C.3,Kammerer Richard A.1,Janke Carsten2,Steinmetz Michel O.1

Affiliation:

1. Biomolecular Research, Paul Scherrer Institut, CH-5232 Villigen PSI, Switzerland

2. Institut Curie, Centre National de la Recherche Scientifique UMR 3306/Institut National de la Santé et de la Recherche Médicale U1005, 91405 Orsay, France

3. Cell Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, Netherlands

Abstract

Tubulin tyrosine ligase (TTL) catalyzes the post-translational retyrosination of detyrosinated α-tubulin. Despite the indispensable role of TTL in cell and organism development, its molecular mechanism of action is poorly understood. By solving crystal structures of TTL in complex with tubulin, we here demonstrate that TTL binds to the α and β subunits of tubulin and recognizes the curved conformation of the dimer. Biochemical and cellular assays revealed that specific tubulin dimer recognition controls the activity of the enzyme, and as a consequence, neuronal development. The TTL–tubulin structure further illustrates how the enzyme binds the functionally crucial C-terminal tail sequence of α-tubulin and how this interaction catalyzes the tyrosination reaction. It also reveals how TTL discriminates between α- and β-tubulin, and between different post-translationally modified forms of α-tubulin. Together, our data suggest that TTL has specifically evolved to recognize and modify tubulin, thus highlighting a fundamental role of the evolutionary conserved tubulin tyrosination cycle in regulating the microtubule cytoskeleton.

Publisher

Rockefeller University Press

Subject

Cell Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3