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Single-particle selection and alignment with heavy atom cluster-antibody conjugates

Jensen, Grant J. and Kornberg, Roger D. (1998) Single-particle selection and alignment with heavy atom cluster-antibody conjugates. Proceedings of the National Academy of Sciences of the United States of America, 95 (16). pp. 9262-9267. ISSN 0027-8424. PMCID PMC21326. doi:10.1073/pnas.95.16.9262.

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A method is proposed for selecting and aligning images of single biological particles to obtain high-resolution structural information by cryoelectron microscopy. The particles will be labeled with multiple heavy atom clusters to permit the precise determination of particle locations and relative orientations even when imaged close to focus with a low electron dose, conditions optimal for recording high-resolution detail. Heavy atom clusters should also allow selection of images free from many kinds of defects, including specimen movement and particle inhomogeneity. Heavy atom clusters may be introduced in a general way by the construction of “adaptor” molecules based on single-chain Fv antibody fragments, consisting of a constant framework region engineered for optimal cluster binding and a variable antigen binding region selected for a specific target. The success of the method depends on the mobility of the heavy atom cluster on the particle, on the precision to which clusters can be located in an image, and on the sufficiency of cluster projections alone to orient and select particles for averaging. The necessary computational algorithms were developed and implemented in simulations that address the feasibility of the method.

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Jensen, Grant J.0000-0003-1556-4864
Additional Information:© 1998, The National Academy of Sciences. Contributed by Roger D. Kornberg, May 26, 1998. We thank Sarah Harris, Dan Millward, Dave Bushnell, Patrice Koehl, Max Vasquez, Jay Tso, and Naoya Tsurushita for helpful discussions. We thank Aaron Klug, Michael Levitt, James Hainfeld, Seth Darst, Ken Downing, and Arun Malhotra for comments on the manuscript. G.J.J. was supported by a Medical Scientist Training Program grant (GM07365) provided by the National Institute of General Medical Sciences at the National Institutes of Health. This research was supported by National Institutes of Health Grant AI21144 to R.D.K. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. §1734 solely to indicate this fact.
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Issue or Number:16
PubMed Central ID:PMC21326
Record Number:CaltechAUTHORS:20181213-110052175
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Official Citation:Single-particle selection and alignment with heavy atom cluster-antibody conjugates Grant J. Jensen, Roger D. Kornberg Proceedings of the National Academy of Sciences Aug 1998, 95 (16) 9262-9267; DOI: 10.1073/pnas.95.16.9262
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91761
Deposited By: George Porter
Deposited On:13 Dec 2018 22:42
Last Modified:16 Nov 2021 03:44

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