Abstract

Electron cryo-microscopy (cryo-EM), particularly single particle cryo-EM, has recently experienced tremendous successes in terms of achievable resolution. It is now possible to determine near atomic structures (< 4 ) of a wide range of biological complexes without crystals, from samples ranging from large viruses with icosahedral symmetry, to ribosomes without symmetry and down to small integral membrane proteins such as ion channels. The goal of this proposal is to establish a high performance Linux computer cluster of 640 CPU cores that is optimized and dedicated to process images for near atomic resolution single particle cryo-EM. Establishing such a computer cluster is a critical step towards routinely determining cryoEM structures at near atomic resolution for a broad array of macromolecular complexes. Many biomedical research projects funded by NIH, particularly those requiring structural determination of previously un-crystallizable complexes, will benefit from such technological advancement. All developed software will be freely provided for research community.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD020054-01
Application #
8826395
Study Section
Special Emphasis Panel (ZRG1-BST-F (30))
Program Officer
Klosek, Malgorzata
Project Start
2015-04-15
Project End
2016-04-14
Budget Start
2015-04-15
Budget End
2016-04-14
Support Year
1
Fiscal Year
2015
Total Cost
$455,590
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

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
Takasaka, Naoki; Seed, Robert I; Cormier, Anthony et al. (2018) Integrin ?v?8-expressing tumor cells evade host immunity by regulating TGF-? activation in immune cells. JCI Insight 3:
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
Palovcak, Eugene; Wang, Feng; Zheng, Shawn Q et al. (2018) A simple and robust procedure for preparing graphene-oxide cryo-EM grids. J Struct Biol 204:80-84

Showing the most recent 10 out of 19 publications