The protein tubulin plays a vital role in the life of all eukaryotic cells. Microtubules, made mostly of tubulin, are involved in organelle movement, separation of chromosomes during cell division, maintenance of cell shape and other critical cellular activities. The assembly and disassembly of microtubules at particular times are essential steps in the cell cycle. These processes are closely regulated, and interference with the regulatory mechanisms can lead to cell death. These properties have made tubulin both a fascinating specimen for biophysical studies and a useful target for anti-cancer drugs. It is important to understand how tubulin molecules interact with each other as well as with large number of other proteins and ligands in these activities in order to have a full understanding of the life of the cell, and as a first step in this direction we have determined the structure of tubulin and microtubules by electron crystallography and cryo-EM. In the proposed work we will extend our understanding of the structure and learn more about the processes that give tubulin its unique properties. We will study the interaction of tubulin with drugs that stabilize microtubules and the interactions with some of the proteins that bind to microtubules and that utilize and regulate the microtubule cytoskeleton. This work will lead to a rational understanding of the functional mechanisms of microtubule dynamics and may reveal several distinct underlying mechanism of microtubule stabilization, eventually allowing development of new, more effective drugs targeted to tubulin.

Public Health Relevance

Our structural studies of tubulin and the microtubules it forms are aimed at understanding how proteins and small ligands interact in regulating processes within cells. This information will expand our knowledge of basic cell biology and enhance opportunities to address diseases including cancer and Parkinson's Disease..

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM051487-18
Application #
8486442
Study Section
Special Emphasis Panel (ZRG1-CB-B)
Project Start
Project End
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
18
Fiscal Year
2013
Total Cost
$408,969
Indirect Cost
$180,929
Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Han, Bong-Gyoon; Watson, Zoe; Kang, Hannah et al. (2016) Long shelf-life streptavidin support-films suitable for electron microscopy of biological macromolecules. J Struct Biol 195:238-44
Hurley, James H; Nogales, Eva (2016) Next-generation electron microscopy in autophagy research. Curr Opin Struct Biol 41:211-216
Borisy, Gary; Heald, Rebecca; Howard, Jonathon et al. (2016) Microtubules: 50 years on from the discovery of tubulin. Nat Rev Mol Cell Biol 17:322-8
Kellogg, Elizabeth H; Howes, Stuart; Ti, Shih-Chieh et al. (2016) Near-atomic cryo-EM structure of PRC1 bound to the microtubule. Proc Natl Acad Sci U S A 113:9430-9
Sun, Jing; Jiang, Xi; Lund, Reidar et al. (2016) Self-assembly of crystalline nanotubes from monodisperse amphiphilic diblock copolypeptoid tiles. Proc Natl Acad Sci U S A 113:3954-9
Berleman, James E; Zemla, Marcin; Remis, Jonathan P et al. (2016) Exopolysaccharide microchannels direct bacterial motility and organize multicellular behavior. ISME J 10:2620-2632
Young, Lindsey N; Cho, Kelvin; Lawrence, Rosalie et al. (2016) Dynamics and architecture of the NRBF2-containing phosphatidylinositol 3-kinase complex I of autophagy. Proc Natl Acad Sci U S A 113:8224-9
Shamir, Eliah R; Coutinho, Kester; Georgess, Dan et al. (2016) Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination. Biol Open 5:1216-28
Jiang, Fuguo; Taylor, David W; Chen, Janice S et al. (2016) Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. Science 351:867-71
Sun, Jing; Jiang, Xi; Siegmund, Aaron et al. (2016) Morphology and Proton Transport in Humidified Phosphonated Peptoid Block Copolymers. Macromolecules 49:3083-3090

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