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bioRxiv · 10.1101/2022.07.04.498718

Effect of Charge Distribution on the Dynamics of Polyampholytic Disordered Proteins

Devarajan, D. S.·Rekhi, S.·Nikoubashman, A.·Kim, Y. C.·Howard, M. P.·Mittal, J.
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Abstract

The stability and physiological function of many biomolecular coacervates depend on the structure and dynamics of intrinsically disordered proteins (IDPs) that typically contain a significant fraction of charged residues. Although the effect of relative arrangement of charged residues on IDP conformation is a well-studied problem, the associated changes in dynamics are far less understood. In this work, we systematically interrogate the effects of charge distribution on the chain-level and segmental dynamics of polyampholytic IDPs in dilute solutions. We study a coarse-grained model polyampholyte consisting of an equal fraction of two oppositely charged residues (glutamic acid and lysine) that undergoes a transition from an ideal chain-like conformation for uniformly charge-patterned sequences to a semi-compact conformation for highly charge-segregated sequences. Changes in the chain-level dynamics with increasing charge segregation correlate with changes in conformation. The chain-level and segmental dynamics conform to simple homopolymer models for uniformly charge-patterned sequences but deviate with increasing charge segregation, both in the presence and absence of hydrodynamic interactions. We discuss the significance of these findings, obtained for a model polyampholyte, in the context of a charge-rich intrinsically disordered region of the naturally occurring protein LAF-1. Our findings have important implications for understanding the effects of charge patterning on the dynamics of polyampholytic IDPs in dilute conditions using polymer scaling theories.

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Devarajan, D. S., Rekhi, S., Nikoubashman, A., Kim, Y. C., Howard, M. P., Mittal, J.. 2022-07-04. Effect of Charge Distribution on the Dynamics of Polyampholytic Disordered Proteins. https://doi.org/10.1101/2022.07.04.498718

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