Jawdat Al-Bassam

Jawdat Al-Bassam

Position Title
Associate Professor

Unit
Department of Molecular and Cellular Biology, College of Biological Sciences

Life Science Addition-3220
Bio

Research Interests

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 αβ-tubulin heterodimers biogenesis inside cells, and how αβ-tubulins are polymerized or depolymerized at microtubule ends.  These molecular machines are found in all eukaryotic organisms and act as αβ-tubulin “factories”, microtubule “polymerases” or “depolymerases” to accelerate specific aspects of microtubule dynamics inside cells.  We also study the mechanism and regulation of kinesin motor proteins involved in organizing microtubules during bipolar spindle assembly during mitosis.  We are focused on deciphering mechanisms of molecular machines and how they cooperate during cell division and development. We combine biochemistry with structural biology approaches such as cryo-electron microscopy (cryo-EM) and X-ray crystallography, and high-resolution single molecule total internal reflection microscopy reconstitution studies to gain a full mechanistic view of structure in relation to function.  Combining these powerful approaches bridges a large resolution range between the αβ-tubulin structure and its polymerization into  microtubules, which span from micro-meter to the sub-nano-meter scales.   These approaches allow us to link  atomic organization and architectures of these molecular machines with αβ-tubulin and their conformational changes with their unique functional states at microtubule ends.

Grad Group Affiliations

  • Biochemistry, Molecular, Cellular and Developmental Biology
  • Biophysics

Specialties / Focus

  • Biochemistry
  • Cell Biology
  • Cell Division and the Cytoskeleton
  • Structural Biology
  • Structural Biology, Membranes and Macromolecular Assembly

Courses

  • MCB 143 Cell and Molecular Biophysics, Spring
  • MCB212 Cell Biology, Winter

Honors and Awards

  • Hellman Fellow University of California Davis, 2014
  • University of California Cancer Research Coordinating Committee Award, 2013-2014
  • National Institutes of Health Pathway to independence award 2008-2014
  • American Cancer Society Postdoctoral Fellowship 2005-2008
  • American Heart Association Predoctoral Fellowship 2000-2003
  • National Institutes of Health Pathway to independence Award 2008-2014
  • California State University President's Scholarship 1995-1998

    Professional Societies

    • American Society of Cell Biology
    • American Biophysical Society

    Degrees

    • 2011 Post Doctoral Fellow Harvard Medical School
    • 2004 PhD Biochemistry and Biophysics Scripps Research Institute
    • 1998 BS Biochemistry California State University Long Beach

    Publications

    Al-Bassam J, Nithianantham S. Malleable folding of coiled-coils regulates kinesin-3 dimerization. Proc Natl Acad Sci U S A. 2018; 115:12845-12847. doi: 10.1073/pnas.1818758115.  

    Nithiananatham S, Cook BD, Beans M, Guo, F, Chang FC, Al-Bassam J.  “Structural Basis of tubulin recruitment and assembly by microtubule polymerases with Tumor Overexpressed Gene (TOG) domain arrays” eLife. pii: e38922. doi: 10.7554/eLife.38922.  

    Nithiananatham S, McNally FJ, Al-Bassam J  “Structural Basis for ATP-dependent oligomerization of the Katanin AAA-ATPase”. J Biol Chem. 2018. 293:10590-605.

     Singh SK, Pandey H, Al-Bassam J, Gheber L“Bidirectional motility of kinesin-5 motor proteins: structural determinants, cumulative functions and physiological roles”.  Cell Mol Life Sci. 2018 75:1757-1771. Review.  

    Al-Bassam, J. (2017). “Revisiting the tubulin cofactors and Arl2 in the regulation of soluble alphabeta-tubulin pools and their effect on microtubule dynamics”. Mol Biol Cell 28, 359-363.

    Shapira, O, Goldstein, A, Al-Bassam J*, and Gheber L*. (2017). “A potential physiological role for bi-directional motility and motor clustering of mitotic kinesin-5 Cin8 in yeast mitosis”. J Cell Sci 130, 725-734. 

    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.

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