Campus Units

Chemistry, Biochemistry, Biophysics and Molecular Biology

Document Type

Article

Publication Version

Published Version

Publication Date

1-7-2016

Journal or Book Title

Chemical Reviews

Volume

116

Issue

11

First Page

6305

Last Page

6322

DOI

10.1021/acs.chemrev.5b00592

Abstract

Solving structures or structural ensembles of large macromolecular systems in solution poses a challenging problem. While NMR provides structural information at atomic resolution, increased spectral complexity, chemical shift overlap, and short transverse relaxation times (associated with slow tumbling) render application of the usual techniques that have been so successful for medium sized systems (<50 >kDa) difficult. Solution X-ray scattering, on the other hand, is not limited by molecular weight but only provides low resolution structural information related to the overall shape and size of the system under investigation. Here we review how combining atomic resolution structures of smaller domains with sparse experimental data afforded by NMR residual dipolar couplings (which yield both orientational and shape information) and solution X-ray scattering data in rigid-body simulated annealing calculations provides a powerful approach for investigating the structural aspects of conformational dynamics in large multidomain proteins. The application of this hybrid methodology is illustrated for the 128 kDa dimer of bacterial Enzyme I which exists in a variety of open and closed states that are sampled at various points in the catalytic cycles, and for the capsid protein of the human immunodeficiency virus.

Comments

This is an article from Venditti, Vincenzo, Timothy K. Egner, and G. Marius Clore. "Hybrid approaches to structural characterization of conformational ensembles of complex macromolecular systems combining NMR residual dipolar couplings and solution X-ray scattering." Chemical reviews 116, no. 11 (2016): 6305-6322. doi:10.1021/acs.chemrev.5b00592. Posted with permission.

Rights

Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.

Language

en

File Format

application/pdf

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