Adenosine Triphosphate; Biochemistry; Biophysics; Kinesin; Crystallography, X-Ray; Cryoelectron Microscopy
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.
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).
Full List of PubMed Publications
- Huehn A, Cao W, Elam WA, Liu X, De La Cruz EM, Sindelar CV: The actin filament twist changes abruptly at boundaries between bare and cofilin-decorated segments. J Biol Chem. 2018 Apr 13; 2018 Feb 20. PMID: 29463680
- Mentes A, Huehn A, Liu X, Zwolak A, Dominguez R, Shuman H, Ostap EM, Sindelar CV: High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing. Proc Natl Acad Sci U S A. 2018 Feb 6; 2018 Jan 22. PMID: 29358376
- Elam WA, Cao W, Kang H, Huehn A, Hocky GM, Prochniewicz E, Schramm AC, Negrón K, Garcia J, Bonello TT, Gunning PW, Thomas DD, Voth GA, Sindelar CV, De La Cruz EM: Phosphomimetic S3D cofilin binds but only weakly severs actin filaments. J Biol Chem. 2017 Dec 1; 2017 Sep 22. PMID: 28939776
- Bell KM, Cha HK, Sindelar CV, Cochran JC: The yeast kinesin-5 Cin8 interacts with the microtubule in a noncanonical manner. J Biol Chem. 2017 Sep 1; 2017 Jul 12. PMID: 28701465
- Sindelar CV, Liu D: Tracking Down Kinesin's Achilles Heel with Balls of Gold. Biophys J. 2017 Jun 20. PMID: 28636903
- Liu D, Liu X, Shang Z, Sindelar CV: Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules. Elife. 2017 May 15; 2017 May 15. PMID: 28504639
- 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