Arginine-phosphate salt bridges between histones and DNA: Intermolecular actuators that control nucleosome architecture

Abstract

Structural bioinformatics and van der Waals density functional theory are combined to investigate the mechanochemical impact of a major class of histone-DNA interactions, namely the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. Principal component analysis reveals that the configurational fluctuations of the sugarphosphate backbone display sequence-specific directionality and variability, and clustering of nucleosomal crystal structures identifies two major salt-bridge configurations: a monodentate form in which the arginine end-group guanidinium only forms one hydrogen bond with the phosphate, and a bidentate form in which it forms two. Density functional theory calculations highlight that the combination of sequence, denticity, and salt-bridge positioning enable the histones to apply a tunable mechanochemical stress to the DNA via precise and specific activation of backbone deformations. The results suggest that selection for specific placements of van der Waals contacts, with high-precision control of the spatial distribution of intermolecular forces, may serve as an underlying evolutionary design principle for the structure and function of nucleosomes, a conjecture that is corroborated by previous experimental studies.

Apolipoprotein E4 inhibits autophagy gene products through direct, specific binding to CLEAR motifs

“…ApoE4–CLEAR sequence modeling reveals close proximity of Arg112 to the phosphate backbone of the CLEAR sequence, but only in the presence of Arg61. This type of interaction is known to stabilize DNA-histone binding [38], especially in the case of two nearby Arg residues [39]. Collectively, these results predict that apoE4 will have stronger CLEAR binding than apoE3 and that this interaction greatly depends on Arg112 and Arg61, suggesting a possible therapeutic target.…”

Impact of Arginine–Phosphate Interactions on the Reentrant Condensation of Disordered Proteins

“…Several proteins bind to DNA through interactions between the phosphate backbone of the DNA and positively charged arginine (Arg) and lysine (Lys) residues. 33 , 34 Despite having similar charges, the interaction between Arg–phosphate is considerably stronger than that of Lys–phosphate. 35 This is because the side chain, guanidinium present on Arg, can form additional interactions with phosphate groups.…”

“… 35 This is because the side chain, guanidinium present on Arg, can form additional interactions with phosphate groups. 33 , 34 The lysozyme’s cationic nature is in part due to an abundance of the solvent-exposed Arg. We hypothesize that the interactions between Arg and the phosphate groups present in TPP and PP may provide the basis for the additional specific attractive interaction that causes the RC of lysozyme by TPP/PP but not by citrate.…”

Mapping of a Regulatory Site of the Escherichia coli ADP-Glucose Pyrophosphorylase

“…It has been established that Arg can have strong electrostatic interactions with phosphates (Woods and Ferre, 2005), forming different types of Arg–phosphate complexes. They could form mono dentate and bidentate interactions (Yusufaly et al, 2014), “forks,” (Calnan et al, 1991) “claws,” (Hamelberg et al, 2007), or “clamps” (Komeda et al, 2011). As an allosteric site example, an Arg cluster has been recognized to be essential in binding the activator glucose 6-phosphate from a Saccharomyces cerevisiae glycogen synthase (Baskaran et al, 2010).…”