Agard, David - University of California, San Francisco - Department of Chemistry and Chemical Biology

研究领域

Our research is focused on elucidating the mechanism of Hsp90 chaperone function and its role in human disease, microtubule nucleation and centrosome structure, and the structure and cell biology of phage-encoded tubulins. In efforts to understand the spatial and temporal regulation of tubulin polymerization into microtubules (MTs), we seek to understand, in atomic detail, the molecular mechanisms underlying dynamic MT behavior and MT nucleation. Accompanying this, is an effort to develop new technologies for high resolution cryoEM and fluorescence light microscopy.

近期论文

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"A bacteriophage tubulin harnesses dynamic instability to center DNA in infected cells," Erb Marcella L; Coker Joanna K C; Chaikeeratisak Vorrapon; Nonejuie Poochit; Pogliano Joe; Kraemer James A; Agard David A, eLife (2014), 3. "Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles," Kirschke, Elaine; Goswami, Devrishi; Southworth, Daniel; Griffin, Patrick R.; Agard, David A., Cell (2014), 157(7), 1685-97. "Microarray-based screening of heat shock protein inhibitors," Emilia Schax, Johanna-Gabriela Walter, Helene Märzhäuser, Frank Stahl, Thomas Scheper, David A. Agard, Simone Eichner, Andreas Kirschning, Carsten Zeilinger, Journal of Biotechnology, (2014), 180, 1-9. "Elucidating the mechanism of substrate recognition by the bacterial Hsp90 molecular chaperone," Street Timothy O; Zeng Xiaohui; Chu Feixia; Pellarin Riccardo; Bonomi Massimiliano; Sali Andrej; Kelly Mark J S; Agard David A, Journal of Molecular Biology (2014), 426(12), 2393-2404. "Sparse labeling of proteins: Structural characterization from long range constraints," Prestegard James H; Agard David A; Lavery Laura A; Moremen Kelley W; Morris Laura C; Pederson Kari, Journal of Magnetic Resonance (2014), 241, 32-40. "The Free Energy Profile of Tubulin Straight-Bent Conformational Changes, with Implications for Microtubule Assembly and Drug Discovery," Lili X. Peng, Monica T. Hsu, Massimiliano Bonomi, David A. Agard, Matthew P. Jacobson, PLoS (2014), e1003464/1-e1003464/13, 13 pp "The Structure and Assembly Mechanism of a Novel Three-Stranded Tubulin Filament that Centers Phage DNA," Elena A. Zehr, James A. Kraemer, Marcella L. Erb, Joanna K.C. Coker, Elizabeth A. Montabana, Joe Pogliano, David A. Agard, Structure (2014), 22(4), 539-548. "Bacterial tubulin TubZ- Bt transitions between a two- stranded intermediate and a four- stranded filament upon GTP hydrolysis," Montabana, Elizabeth A.; Agard, David A., Proceedings of the National Academy of Sciences of the United States of America (2014), 111(9), 3407-3412 "Structural Asymmetry in the Closed State of Mitochondrial Hsp90 (TRAP1) Supports a Two-Step ATP Hydrolysis Mechanism," Laura A. Lavery, James R. Partridge, Theresa A. Ramelot, Daniel Elnatan, Michael A. Kennedy, David A. Agard, Molecular Cell, Volume 53, Issue 2, 23 January 2014, Pages 330-343 "Cell-cycle regulation of formin-mediated actin cable assembly," Miao Y, Wong CC, Mennella V, Michelot A, Agard DA, Holt LJ, Yates JR 3rd, Drubin DG., Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4446-55 "Amorphous no more: subdiffraction view of the pericentriolar material architecture," Vito Mennella, David A. Agard, Bo Huang, Laurence Pelletier, Trends in Cell Biology, 2013. "High-resolution restoration of 3D structrues from widefield images wiht extreme low signal-to-noise ratio," Muthuvel Arigovindan, Jennifer C. Fung, Daniel Elnatan, Vito Mennella, Yee-Hung Mark Chan, Michael Pollard, Eric Branlund, John W. Sedat, and David A. Agard, Proc Nat Assoc Sci., 2013, Oct 22, 110(43), 17344-9. "Influence of electron dose rate on electron counting images recorded with the K2 camera," Li X, Zheng SQ, Egami K, Agard DA, Cheng Y., J Struct Biol. 2013 Aug 20 "Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM," Li, Xueming; Mooney, Paul; Zheng, Shawn; Booth, Christopher R.; Braunfeld, Michael B.; Gubbens, Sander; Agard, David A.; Cheng, Yifan, Nature Methods (2013), 10(6), 584-590. "The bacterial actin MamK: in vitro assembly behavior and filament architecture," Ozyamak E, Kollman J, Agard DA, Komeili A., J Biol Chem. 2013, 288(6), 4265-77. "Uncovering a region of heat shock protein 90 important for client binding in E. coli and chaperone function in yeast." Genest O, Reidy M, Street TO, Hoskins JR, Camberg JL, Agard DA, Masison DC, Wickner S., Mol Cell. 2013, 49(3), 464-73. "Fast multicolor 3D imaging using aberration-corrected multifocus microscopy," Sara Abrahamsson, Jiji Chen, Bassam Hajj, Sjoerd Stallinga, Alexander Y Katsov, Jan Wisniewski, Gaku Mizuguchi, Pierre Soule, Florian Mueller, Claire Dugast Darzacq, Xavier Darzacq, Carl Wu , Cornelia I Bargmann , David A Agard , Maxime Dahan, & Mats G L Gustafsson, Nature Methods, 2013, 10(1), 60-3 "Subdiffraction-resolution fluorescence microscopy reveals a domain of the centrosome critical for pericentriolar material organization," Mennella V, Keszthelyi B, McDonald KL, Chhun B, Kan F, Rogers GC, Huang B and Agard DA, Nature Cell Biology, 2012, 14, 1159-68. "The bacterial actin MamK: in vitro assembly behavior and filament architecture," Ertan Ozyamak, Justin Kollman, David A. Agard, and Arash Komeili, J. Biological Chem., Nov 2012. "A Method for Integrative Structure Determination of Protein-Protein Complexes," Schneidman-Duhovny Dina; Rossi Andrea; Avila-Sakar Agustin; Kim Seung Joong; Velazquez-Muriel Javier; Strop Pavel; Liang Hong; Krukenberg Kristin A; Liao Maofu; Kim Ho Min; Sobhanifar Solmaz; Dötsch Volker; Rajpal Arvind; Pons Jaume; Agard David A; Cheng Yifan; and Sali Andrej, Bioinformatics (Oxford, England) (2012) "A phage tubulin assembles dynamic filaments by a novel mechanism to center viral DNA within the host cell," J. Kraemer, M.L. Erb, C.A. Waddling, E.A. Montabana, E.A. Zehr, H. Wang, K. Nguyen, D.S.L. Pham, D. Agard, and J. Pogliano, Cell, 2012, 149(7), 1488-99