Al-Bassam, Jawdat - University of California, Davis

研究领域

The Structure and Mechanisms of Microtubule Regulatory Proteins in Assembly and Disassembly of tubulin dimers Microtubules are dynamic protein polymers that generate forces inside eukaryotic cells that lead to transformations to divide, develop, or crawl. Microtubules assemble from basic building blocks, known as alpha beta (αβ) tubulin dimers, which polymerize head-to-tail to form protofilaments, using the energy of Guanosine 3,5 Triphosphate (GTP) binding and hydrolysis; These protofilaments associate laterally enclosing a tube-like structure-- a microtubule. Tubulin polymerization is driven by its high concentration inside the cytoplasm and activates GTP hydrolysis upon its incorporation into microtubule lattices at their ends. However, during stochastic reversals, called catastrophes, tubulin protofilaments stop polymerizing and peel-out to rapidly dissemble microtubules. The Al-Bassam laboratory studies conserved multi-subunit molecular machines drive soluble ab-tubulin heterodimers biogenesis inside cells, and how ab-tubulins are polymerized or depolymerized at microtubule ends. These molecular machines are found in all eukaryotic organisms and act as ab-tubulin “factories”, microtubule “polymerases” or “depolymerases” to accelerate specific aspects of microtubule dynamics inside cells. We are focused on deciphering mechanisms of these machines and how they cooperate during cell division and development. We combine biochemistry, structural biology approaches such as electron microscopy and X-ray crystallography with high-resolution single molecule total internal reflection microscopy to study the structure and regulation of microtubule dynamics. These powerful approaches bridge the large resolution range between ab-tubulin structure and its polymerization into dynamic microtubules, which span micro-meters to the sub-nanometers. These approaches allow us to link atomic architectures of these molecular machines with ab-tubulin and their conformational changes during unique functional states at microtubule ends.

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Nithiananatham S, Le S, Seto E, Jia W, Leary J, Corbett KD, Moore JK, Al-Bassam J Tubulin Cofactors and Arl2 are Cage-like Chaperones that regulate the soluble αβ-Tubulin pool for Microtubule Dynamics. eLife (Cambridge) 2015;10.7554/eLife.08811 Scholey J.E., Nithiananatham S., Scholey J.M., Al-Bassam J. “The structural basis for the Assembly of the Mitotic Motor Kinesin-5 into Bipolar Tetramers”. Elife (Cambridge). 2014. 3:e02217. doi: 10.7554/elife.02217 Al-Bassam J. ”Reconstituting Dynamic Microtubule Polymerization Regulation by TOG Domain Proteins”. Methods in Enzymology. 2014. 540: 131-14 Al-Bassam J. ”Reconstituting Dynamic Microtubule Polymerization Regulation by TOG Domain Proteins”. Methods in Enzymology. 2014. 540: 131-14 Al-Bassam J., Corbett K. α-Tubulin Acetylation from the inside out . PNAS. 2012. 109:19515-19516. Al-Bassam J., Kim H., Flor-Parra I., Lal N., Velji H., Chang F. Fission yeast Alp14 is a Dose Dependent Plus end-tracking Microtubule Polymerase. Mol Biol Cell. 23:2878-2890. Al-Bassam J , Chang F. Regulation of Microtubule dynamics by TOG domain proteins XMAP215/Dis1 and CLASP. Trends in Cell Biology, 2011. 21 (10): 604-614 Al-Bassam J , Kim H, Brouhard G, van Oijen A, Harrison SC, Chang F. CLASP promotes microubule rescues by recruiting tubulin dimer to the microtubule” . Developmenal Cell, 2010. 19 (2): 245--258 Brouhard G*, Stear J* , Notzel T, Al-Bassam J, Kinoshita K, Harrison SC, Howard J, Hyman AA, XMAP215 is a processive microtubule polymerase that catalyzes both growth and shrinkage, Cell. 2008, 132(1):79-88; Al-Bassam J, Larsen NA, Hyman AA, Harrison SC. Crystal structure of a TOG domain: conserved features of XMAP215/Dis1-family TOG domains and implications for tubulin binding. Structure. 2007 Mar; 15(3):355-62. Al-Bassam J, Roger B, Halpain S, Milligan RA. Analysis of the weak interactions of ADP-Unc104 and ADP-kinesin with microtubules and their inhibition by MAP2c. Cell Motil Cytoskeleton. 2007 May;64(5):377-89 Larsen NA, Al-Bassam J, Wei RR, Harrison SC. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1201-6. Wei RR, Al-Bassam J, Harrison SC. The Ndc80/HEC1 complex is a contact point for kinetochoremicrotubule attachment. Nat Struct Mol Biol. 2007 Jan;14(1):54-9. Al-Bassam J*, van Breugel M*, Harrison SC, Hyman A. Stu2p binds tubulin and undergoes an open-to closed conformational change. J Cell Biol. 2006 Mar 27; 172:1009-22. Roger. B*, Al-Bassam J.*, Milligan R.A., Halpain S. MAP2, but not tau, repeats bind and bundle factin, Current Biol. 2004. 14:363-371 Al-Bassam J.*, Cui Y.*, Klopheinstein D., Carragher, B.O., Vale R.D., Milligan, R.A. Distinct Conformations of the Kinesin Unc104 Neck Regulate a Monomer-to-Dimer Motor Transition, J. CellBiol. 2003. 163: 743-753. Al-Bassam J., Ozer R.S., Safer D., Halpain S., Milligan R.A.; MAP2 and tau bind along the outer ridges of microtubule protofilaments. 2002. J. Cell Biol. 157: 1187-1196.