The Disordered Spindly C-terminus Interacts with RZZ Subunits ROD-1 and ZWL-1 in the Kinetochore through the Same Sites in C. Elegans |
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| Institution: | 1. University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA;2. Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;3. Anderson University, Department of Chemistry and Biology, 316 Boulevard, Anderson, SC 29621, USA;1. Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;2. Departments of Biochemistry, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;3. Medicine, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;4. Oncology, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;5. Department of Biology, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada;6. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada;1. Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA;2. The Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA;3. Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA;4. The Biophysics Collaborative Access Team (BioCAT), Department of Biological Chemical and Physical Sciences, Illinois Institute of Technology, Chicago, IL 60616, USA;5. University of California Los Angeles, Los Angeles, CA 90095, USA;6. Department of Biochemistry and the Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA;1. Graduate Institute of Biochemistry, National Chung Hsing University, Taichung City 40227, Taiwan, ROC;2. Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC;3. Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung City 40227, Taiwan, ROC;4. Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, 145 Xinda Rd., South Dist., Taichung City 40227, Taiwan, ROC;5. Ph.D. Program in Transnational Medicine, National Chung Hsing University, 145 Xinda Rd., South Dist., Taichung City 40227, Taiwan, ROC;1. Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany;2. Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Universitätsstrasse, 45141 Essen, Germany;1. Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR 97331, USA;2. Department of Chemistry & Biochemistry, University of Oregon, Eugene, OR 97403, USA;3. Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA;4. Materials Science Institute, University of Oregon, Eugene, OR 97403, USA |
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| Abstract: | Spindly is a dynein adaptor involved in chromosomal segregation during cell division. While Spindly's N-terminal domain binds to the microtubule motor dynein and its activator dynactin, the C-terminal domain (Spindly-C) binds its cargo, the ROD/ZW10/ZWILCH (RZZ) complex in the outermost layer of the kinetochore. In humans, Spindly-C binds to ROD, while in C. elegans Spindly-C binds to both Zwilch (ZWL-1) and ROD-1. Here, we employed various biophysical techniques to characterize the structure, dynamics and interaction sites of C. elegans Spindly-C. We found that despite the overall disorder, there are two regions with variable α-helical propensity. One of these regions is located in the C-terminal half and is compact; the second is sparsely populated in the N-terminal half. The interactions with both ROD-1 and ZWL-1 are mostly mediated by the same two sequentially remote disordered segments of Spindly-C, which are C-terminally adjacent to the helical regions. The findings suggest that the Spindly-C binding sites on ROD-1 in the ROD-1/ZWL-1 complex context are either shielded or conformationally weakened by the presence of ZWL-1 such that only ZWL-1 directly interacts with Spindly-C in C. elegans |
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| Keywords: | Spindly ROD/ZW10/ZWILCH RZZ Nuclear magnetic resonance Intrinsically disordered protein |
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