The Harvard Center for Cryo-Electron Microscopy (HC2EM) is a joint effort by Harvard Medical School, Dana-Farber Cancer Institute, Boston Children’s Hospital, and Massachusetts General Hospital to provide state-of-the-art cryo-EM instrumentation and expertise for the Harvard structural biology community. This user facility offers consultation and training by staff in specimen preparation, microscope operation, image acquisition, and data analysis. 

Additionally, the Molecular Electron Microscopy Suite (MEMS) at Harvard Medical School is a separate user resource currently available to qualified researchers affiliated with Quad-based labs at HMS. This separate resource offers training and supervision in negative-stain and cryo-transmission electron microscopy. Equipment includes four transmission electron microscopes, two cryo plungers, and sample preparation areas. 

Recent Blog Updates

Recent Publications

François A. Thélot, Wenyi Zhang, KangKang Song, Chen Xu, Jing Huang, and Maofu Liao. 9/23/2021. “Distinct allosteric mechanisms of first-generation MsbA inhibitors.” Science.Abstract
ATP-binding cassette (ABC) transporters couple ATP hydrolysis to substrate transport across biological membranes. Although many are promising drug targets, their mechanisms of modulation by small molecule inhibitors remain largely unknown. Intriguingly, two first-generation inhibitors of the MsbA transporter, TBT1 and G247, induce opposite effects on ATP hydrolysis. Using single-particle cryo-electron microscopy and functional assays, we show that TBT1 and G247 bind adjacent yet separate pockets in the MsbA transmembrane domains. Two TBT1 molecules asymmetrically occupy the substrate binding site, leading to a collapsed inward-facing conformation with decreased distance between the nucleotide-binding domains (NBDs). In contrast, two G247 molecules symmetrically increases NBD distance in a wide inward-open state of MsbA. The divergent mechanisms of action of these MsbA inhibitors provide important insights into ABC transporter pharmacology.
Yun Quan, Stephen M. Hinshaw, Pang-Che Wang, Stephen C. Harrison, and Huilin Zhou. 6/3/2021. “Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore.” Journal of Cell Biology, 220, 8. Publisher's VersionAbstract
The step-by-step process of chromosome segregation defines the stages of the cell cycle. In eukaryotes, signals controlling these steps converge upon the kinetochore, a multiprotein assembly that connects spindle microtubules to chromosomal centromeres. Kinetochores control and adapt to major chromosomal transactions, including replication of centromeric DNA, biorientation of sister centromeres on the metaphase spindle, and transit of sister chromatids into daughter cells during anaphase. Although the mechanisms that ensure tight microtubule coupling at anaphase are at least partly understood, kinetochore adaptations that support other cell cycle transitions are not. We report here a mechanism that enables regulated control of kinetochore sumoylation. A conserved surface of the Ctf3/CENP-I kinetochore protein provides a binding site for Ulp2, the nuclear enzyme that removes SUMO chains from modified substrates. Ctf3 mutations that disable Ulp2 recruitment cause elevated inner kinetochore sumoylation and defective chromosome segregation. The location of the site within the assembled kinetochore suggests coordination between sumoylation and other cell cycle–regulated processes.

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A Better Look: The development of cryo-EM has revolutionized structural biology

September 12, 2018
"Throughout history, observations of structure, from Hooke’s cells to the beaks of Darwin’s finches, have provided insights necessary to understand how life works. This is particularly true in structural biology, a discipline focused on visualizing life at its most fundamental. Discoveries of the atomic structures of important proteins and biological molecules have been among the most celebrated in science and have generated more than a dozen Nobel Prizes, new fields of research, and multibillion-dollar companies."

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