This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Kinesin-1 is a motor protein that hydrolyzes ATP to drive the transport of intracellular cargo. It is composed of two heavy chains (KHCs) and two light chains (KLCs). Proper regulation of kinesin-1 prevents mislocalization of the motor and allows for coordination with other molecular motors. Regulated kinesin-1 is folded in half so that the KLCs and regulatory KHC tail domains come in contact with the enzymatically active KHC heads. This KHC/KLC complex is central to the regulatory mechanism of kinesin-1, yet the structure remains undetermined because the complex is not amenable to traditional structure determination techniques. To overcome this, we will use small-angle X-ray scattering (SAXS) to visualize the never-before-seen structure of a regulated kinesin-1 holoenzyme in solution at ~3nm resolution. Active kinesin-1 has significant structural variability, and we expect that only a radius of gyration for the entire extended molecule will be obtained. However, the regulated conformation appears to be a compact and rigid structure, therefore, we expect to obtain valuable information about the molecular shape of regulated kinesin-1 from SAXS. Together with chemical crosslinking studies, we will use the SAXS structure to determine where the various kinesin-1 elements interact with each other in this regulated complex. During our first session, we were able to collect sample data but subsequent analysis determined that the camera length was too short for optimum structure determination. We are scheduled to repeat our experiments with a longer camera on Nov 21, and we anticipate that this will yield the desired data.
| 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 |
| 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 |
| 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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