This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Significance: Centrioles are small cylindrical organelles (~100 nm in diameter and ~150 nm in length) whose main distinguishing characteristic is a 9-fold symmetric array of stabilized microtubules. Centrioles have two key functions in eukaryotic cells: (1) They recruit pericentriolar material (PCM) to form centrosomes and (2) they template the formation of cilia. In dividing cells, centrioles, like nuclear DNA, duplicate precisely once per cell cycle in a process that initiates during S-phase. During duplication a single new centriole forms adjacent and at right angles to each parent centriole. Despite their importance, the process of centriole assembly remains largely mysterious. Critical questions include: How is the 9-fold symmetry of the centriole dictated? What limits centriole assembly to a single centriole in the vicinity of the parent? How is centriole length so precisely controlled? Recently, the emergence of Caenorhabditis elegans as a model system provided a major breakthrough in understanding this process by defining a small set of components that constitute the core centriole duplication machinery. Genome wide analysis in C. elegans identified four proteins specifically required for centriole assembly: ZYG-1, SAS-4, SAS-5, and SAS-6. ZYG-1 is a polo family kinase that is thought to play a signaling role to coordinate duplication with the cell cycle and ensure formation adjacent to the parent. SAS-4 and SAS-6 are widely conserved and are thought to be core structural components of the centriole. The work proposed here centers on SAS-6, which is thought to be a component of the first identifiable structural intermediate in centriole assembly, a structure called the central tube/cartwheel. This structural intermediate consists of a nine-fold symmetric array of spokes that emanate from a central tubule. The goal of the proposed work is to use electron microscopy to characterize the structure and assembly of SAS-6 in vitro.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-CB-B (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Scripps Research Institute
La Jolla
United States
Zip Code
Kulczyk, Arkadiusz W; Moeller, Arne; Meyer, Peter et al. (2017) Cryo-EM structure of the replisome reveals multiple interactions coordinating DNA synthesis. Proc Natl Acad Sci U S A 114:E1848-E1856
Sherman, Michael B; Kakani, Kishore; Rochon, D'Ann et al. (2017) Stability of Cucumber Necrosis Virus at the Quasi-6-Fold Axis Affects Zoospore Transmission. J Virol 91:
Short, James R; Speir, Jeffrey A; Gopal, Radhika et al. (2016) Role of Mitochondrial Membrane Spherules in Flock House Virus Replication. J Virol 90:3676-83
Razinkov, Ivan; Dandey, Venkat; Wei, Hui et al. (2016) A new method for vitrifying samples for cryoEM. J Struct Biol 195:190-198
Guenaga, Javier; de Val, Natalia; Tran, Karen et al. (2015) Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. PLoS Pathog 11:e1004570
McCullough, John; Clippinger, Amy K; Talledge, Nathaniel et al. (2015) Structure and membrane remodeling activity of ESCRT-III helical polymers. Science 350:1548-51
McNulty, Reginald; Lokareddy, Ravi Kumar; Roy, Ankoor et al. (2015) Architecture of the Complex Formed by Large and Small Terminase Subunits from Bacteriophage P22. J Mol Biol 427:3285-3299
Lee, Jeong Hyun; Leaman, Daniel P; Kim, Arthur S et al. (2015) Antibodies to a conformational epitope on gp41 neutralize HIV-1 by destabilizing the Env spike. Nat Commun 6:8167
Derking, Ronald; Ozorowski, Gabriel; Sliepen, Kwinten et al. (2015) Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLoS Pathog 11:e1004767
Grover, Rajesh K; Zhu, Xueyong; Nieusma, Travis et al. (2014) A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union. Science 343:656-661

Showing the most recent 10 out of 187 publications