This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Physiological functions that involve cellular shape rearrangement and/or cellular motilityrequire spatial and temporal changes in the assembly and disassembly of filamentous (F-) actinfrom pools of monomeric (globular, G-) actin within the cell's cytoskeleton. This process istightly regulated by various actin-binding proteins, such as gelsolin, which generally act inresponse to specific cell signals, such as an increase in cellular Ca2+ levels. Gelsolinregulation of actin is under the control of Ca2+ and poly-phosphoinositides and includessevering, capping, and nucleation of filaments. Work from several research groups has shownthat Ca2+ regulation of gelsolin is complex and that certain functions are activated in the 1micromolar range whereas others are activated at higher concentrations (10 ? 1000 micromolar).The main aim of our proposed SAXS experiment is to follow the structural changes during depolymerizationof F-actin when in the presence of gelsolin and as a function of Ca2+concentration. We propose to collect SAXS data on samples of filamentous F-actin and Factin:gelsolin complexes at varying molar ratios (from 1:20 to 1:1) of gelsolin:actin and at 5levels of calcium concentrations (0, 0.1, 1.0, 100 and 1000 micromolar). These data will beanalyzed by typical SAXS analysis tools such as Porod and Guinier approximation, IndirectFourier Transform methods and molecular modeling. Results will aid in the elucidation of amechanism for actin de-polymerization by gelsolin, providing a structural basis forunderstanding how the continuous reorganization of actin filaments is controlled by specificprotein-protein interactions.
| Sullivan, Brendan; Robison, Gregory; Pushkar, Yulia et al. (2017) Copper accumulation in rodent brain astrocytes: A species difference. J Trace Elem Med Biol 39:6-13 |
| Orgel, Joseph P R O; Sella, Ido; Madhurapantula, Rama S et al. (2017) Molecular and ultrastructural studies of a fibrillar collagen from octocoral (Cnidaria). J Exp Biol 220:3327-3335 |
| Yazdi, Aliakbar Khalili; Vezina, Grant C; Shilton, Brian H (2017) An alternate mode of oligomerization for E. coli SecA. Sci Rep 7:11747 |
| Morris, Martha Clare (2016) Nutrition and risk of dementia: overview and methodological issues. Ann N Y Acad Sci 1367:31-7 |
| Robison, Gregory; Sullivan, Brendan; Cannon, Jason R et al. (2015) Identification of dopaminergic neurons of the substantia nigra pars compacta as a target of manganese accumulation. Metallomics 7:748-55 |
| Gelfand, Paul; Smith, Randy J; Stavitski, Eli et al. (2015) Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed FTIR Imaging. Anal Chem 87:6025-31 |
| Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-1358 |
| Zhou, Hao; Li, Shangyang; Badger, John et al. (2015) Modulation of HIV protease flexibility by the T80N mutation. Proteins 83:1929-39 |
| Nobrega, R Paul; Arora, Karunesh; Kathuria, Sagar V et al. (2014) Modulation of frustration in folding by sequence permutation. Proc Natl Acad Sci U S A 111:10562-7 |
| Jiao, Lianying; Ouyang, Songying; Shaw, Neil et al. (2014) Mechanism of the Rpn13-induced activation of Uch37. Protein Cell 5:616-30 |
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