Sindelar, Chuck V - Yale University - Biological & Biomedical Sciences

个人简介

My scientific career has largely focused on developing an atomic-level understanding of a model cytoskeletal system, the kinesin molecular motor which transports cargo along microtubules. While my Ph.D. work emphasized X-ray crystallography and EPR spin-labeling techniques as applied to the kinesin system, my more recent work has turned towards advancing cryo-electron microscopy techniques to the point where atomic-level features can be obtained for systems such as cytoskeletal filaments. These efforts led to my recent synthesis, using cryo-electron microscopy (cryo-EM) and X-ray crystallography information, of an atomic-level model for kinesin’s ATP-sensing machinery in its active form, which is only assumed following microtubule attachment. This discovery led to a simple and intuitive “seesaw” mechanism describing how ATP binding leads to force generation in the microtubule-attached motor. My laboratory's research interests are rapidly expanding to include numerous other filament-related molecular machines, such the myosin molecular motor that powers muscle movement, and diverse protein machinery involved in DNA repair and splicing. PhD University of California at San Francisco (2002) BS Massachusetts Institute of Technology (1992)

研究领域

Adenosine Triphosphate; Biochemistry; Biophysics; Kinesin; Crystallography, X-Ray; Cryoelectron Microscopy

近期论文

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An adaptation of the Wiener filter suitable for analyzing images of isolated single particles. C. Sindelar; N. Grigorieff. An adaptation of the Wiener filter suitable for analyzing images of isolated single particles. J. Struct. Biol. 176:60-74 (2011). A seesaw model for intermolecular gating in the kinesin motor protein. C. Sindelar. A seesaw model for intermolecular gating in the kinesin motor protein. Biophysical Reviews 3:85-100 (2011). An atomic-level mechanism for activation of the kinesin molecular motors. Sindelar*; K. Downing. An atomic-level mechanism for activation of the kinesin molecular motors. PNAS 107:4111-4116 (2010). ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement. Cochran; C. Sindelar; N. Mulko; K. Collins; S. Kong; R. Hawley; F. J. Kull. ATPase Cycle of the Nonmotile Kinesin NOD Allows Microtubule End Tracking and Drives Chromosome Movement. Cell 136(1):110-22 (2009). The Beginning of Kinesin’s Force-Generating Cycle Visualized at 9 Å Resolution. C. Sindelar; K. Downing. The Beginning of Kinesin’s Force-Generating Cycle Visualized at 9 Å Resolution. J. Cell. Biol. 177(3): 377-85 (2007). Ropars V, Yang Z, Isabet T, Blanc F, Zhou K, Lin T, Liu X, Hissier P, Samazan F, Amigues B, Yang ED, Park H, Pylypenko O, Cecchini M, Sindelar CV, Sweeney HL, Houdusse A: The myosin X motor is optimized for movement on actin bundles. Nat Commun. 2016 Sep 1; 2016 Sep 1. PMID: 27580874 Zanetti MN, Bello OD, Wang J, Coleman J, Cai Y, Sindelar CV, Rothman JE, Krishnakumar SS: Ring-like oligomers of Synaptotagmins and related C2 domain proteins. Elife. 2016 Jul 19; 2016 Jul 19. PMID: 27434670 Kang H, Bradley MJ, Cao W, Zhou K, Grintsevich EE, Michelot A, Sindelar CV, Hochstrasser M, De La Cruz EM: Site-specific cation release drives actin filament severing by vertebrate cofilin. Proc Natl Acad Sci U S A. 2014 Dec 16; 2014 Dec 2. PMID: 25468977 Shang Z, Zhou K, Xu C, Csencsits R, Cochran JC, Sindelar CV: High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force-generation. Elife. 2014 Nov 21; 2014 Nov 21. PMID: 25415053 Wang J, Bello O, Auclair SM, Wang J, Coleman J, Pincet F, Krishnakumar SS, Sindelar CV, Rothman JE: Calcium sensitive ring-like oligomers formed by synaptotagmin. Proc Natl Acad Sci U S A. 2014 Sep 23; 2014 Sep 8. PMID: 25201968 Shen QT, Hsiue PP, Sindelar CV, Welch MD, Campellone KG, Wang HW: Structural insights into WHAMM-mediated cytoskeletal coordination during membrane remodeling. J Cell Biol. 2012 Oct 1. PMID: 23027905 Sindelar CV, Grigorieff N: Optimal noise reduction in 3D reconstructions of single particles using a volume-normalized filter. J Struct Biol. 2012 Oct; 2012 May 18. PMID: 22613568 Sindelar CV: A seesaw model for intermolecular gating in the kinesin motor protein. Biophys Rev. 2011 Jun; 2011 Jun 4. PMID: 21765878