Electron cryo-microscopy (cryo-EM), particularly single particle cryo-EM, has experienced tremendous successes in term of achievable resolution. It is now possible to determine near atomic resolution structures of a wide range of biological complexes without crystals, from as large as viruses with icosahedral symmetry, to ribosomal particles without symmetry to small integral membrane proteins such as ion channels. We have made tremendous contributions to the cryo-EM technological breakthroughs and our successes generated unprecedented high demands from many laboratories at UCSF to access cryo-EM for their NIH funded structural biology projects. The goal of this proposal is to acquire a high performance electron cryo-microscope system for efficient high-resolution data acquisition. Setting up such a high-end cryo-EM system will enable us to take full advantage of recent technological breakthroughs in single particle cryo-EM to study structures of a wide range of challenging biological macromolecules. Many biomedical research projects funded by NIH, particularly those requiring structural determination of large complexes, will benefit from availability of such a state-of-the-art cryo- EM instrument.

Public Health Relevance

Structural study of protein complexes is of vital importance in understanding the mechanisms of many human diseases. Recent technological breakthrough, partly contributed by our laboratories at University of California San Francisco, transformed electron cryo-microscopy (cryo-EM), especially single particle cryo-EM, to a powerful technique for the high-resolution structure determination of protein complexes. It also generated unprecedented high demands to access cryo-EM technology from structural biology community. This application is to obtain a high-performance electron cryo-microscope system for efficient data acquisition for the purpose of routinely determining structures of many large protein complexes towards near atomic resolution. It will accommodate the needs of high-end cryo-EM instrumentation by NIH funded biomedical research projects.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Biomedical Research Support Shared Instrumentation Grants (S10)
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Special Emphasis Panel (ZRG1)
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Levy, Abraham
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Cormier, Anthony; Campbell, Melody G; Ito, Saburo et al. (2018) Cryo-EM structure of the ?v?8 integrin reveals a mechanism for stabilizing integrin extension. Nat Struct Mol Biol 25:698-704
Kintzer, Alexander F; Green, Evan M; Dominik, Pawel K et al. (2018) Structural basis for activation of voltage sensor domains in an ion channel TPC1. Proc Natl Acad Sci U S A 115:E9095-E9104
Kalia, Raghav; Wang, Ray Yu-Ruei; Yusuf, Ali et al. (2018) Structural basis of mitochondrial receptor binding and constriction by DRP1. Nature 558:401-405
Autzen, Henriette E; Myasnikov, Alexander G; Campbell, Melody G et al. (2018) Structure of the human TRPM4 ion channel in a lipid nanodisc. Science 359:228-232
Zhang, Yunxiao; Bulkley, David P; Xin, Yao et al. (2018) Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched. Cell 175:1352-1364.e14
Cheng, Yifan (2018) Single-particle cryo-EM-How did it get here and where will it go. Science 361:876-880
Tsai, Jordan C; Miller-Vedam, Lakshmi E; Anand, Aditya A et al. (2018) Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule. Science 359:
Cheng, Yifan (2018) Membrane protein structural biology in the era of single particle cryo-EM. Curr Opin Struct Biol 52:58-63
Nguyen, Nam X; Armache, Jean-Paul; Lee, Changkeun et al. (2018) Cryo-EM structure of a fungal mitochondrial calcium uniporter. Nature 559:570-574
Hohendahl, Annika; Talledge, Nathaniel; Galli, Valentina et al. (2017) Structural inhibition of dynamin-mediated membrane fission by endophilin. Elife 6: