期刊
JOURNAL OF STRUCTURAL BIOLOGY
卷 209, 期 1, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jsb.2019.107416
关键词
Cryo-electron microscopy; Methods development; Image processing; Multiple structures; Classification; Heterogeneous mixtures
资金
- Welch Foundation [F-1938, F-1515]
- Army Research Office [W911NF-15-1-0120, W911NF-19-1-0021]
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation Medical Research Award
- National Institutes of Health [GM122480, DK110520, HD085901]
- Cancer Prevention and Research Institute of Texas [RR160088]
Single particle analysis for structure determination in cryo-electron microscopy is traditionally applied to samples purified to near homogeneity as current reconstruction algorithms are not designed to handle heterogeneous mixtures of structures from many distinct macromolecular complexes. We extend on long established methods and demonstrate that relating two-dimensional projection images by their common lines in a graphical framework is sufficient for partitioning distinct protein and multiprotein complexes within the same data set. The feasibility of this approach is first demonstrated on a large set of synthetic reprojections from 35 unique macromolecular structures spanning a mass range of hundreds to thousands of kilodaltons. We then apply our algorithm on cryo-EM data collected from a mixture of five protein complexes and use existing methods to solve multiple three-dimensional structures ab initio. Incorporating methods to sort single particle cryo-EM data from extremely heterogeneous mixtures will alleviate the need for stringent purification and pave the way toward investigation of samples containing many unique structures.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据