Integrating NMR, SAXS, and Atomistic Simulations: Structure and Dynamics of a Two-Domain Protein

Biophysical Journal
Karl T DebiecAngela M Gronenborn

Abstract

Multidomain proteins with two or more independently folded functional domains are prevalent in nature. Whereas most multidomain proteins are linked linearly in sequence, roughly one-tenth possess domain insertions where a guest domain is implanted into a loop of a host domain, such that the two domains are connected by a pair of interdomain linkers. Here, we characterized the influence of the interdomain linkers on the structure and dynamics of a domain-insertion protein in which the guest LysM domain is inserted into a central loop of the host CVNH domain. Expanding upon our previous crystallographic and NMR studies, we applied SAXS in combination with NMR paramagnetic relaxation enhancement to construct a structural model of the overall two-domain system. Although the two domains have no fixed relative orientation, certain orientations were found to be preferred over others. We also assessed the accuracies of molecular mechanics force fields in modeling the structure and dynamics of tethered multidomain proteins by integrating our experimental results with microsecond-scale atomistic molecular dynamics simulations. In particular, our evaluation of two different combinations of the latest force fields and water models revealed...Continue Reading

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Citations

Jul 11, 2019·Journal of the Royal Society, Interface·Sophie Sacquin-Mora
Jan 14, 2021·Analytical Chemistry·Yunfei HuMaili Liu
Jul 27, 2021·Biophysical Journal·Maximilia F de Souza DegenhardtRoberto K Salinas
May 31, 2018·The Journal of Physical Chemistry. B·O H Samuli OllilaHideo Iwaï

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