DNA–protein π-interactions in nature: abundance, structure, composition and strength of contacts between aromatic amino acids and DNA nucleobases or deoxyribose sugar

Abstract

Four hundred twenty-eight high-resolution DNA–protein complexes were chosen for a bioinformatics study. Although 164 crystal structures (38% of those searched) contained no interactions, 574 discrete π–contacts between the aromatic amino acids and the DNA nucleobases or deoxyribose were identified using strict criteria, including visual inspection. The abundance and structure of the interactions were determined by unequivocally classifying the contacts as either π–π stacking, π–π T-shaped or sugar–π contacts. Three hundred forty-four nucleobase–amino acid π–π contacts (60% of all interactions identified) were identified in 175 of the crystal structures searched. Unprecedented in the literature, 230 DNA–protein sugar–π contacts (40% of all interactions identified) were identified in 137 crystal structures, which involve C–H···π and/or lone–pair···π interactions, contain any amino acid and can be classified according to sugar atoms involved. Both π–π and sugar–π interactions display a range of relative monomer orientations and therefore interaction energies (up to –50 (–70) kJ mol−1 for neutral (charged) interactions as determined using quantum chemical calculations). In general, DNA–protein π-interactions are more prevalent than perhaps currently accepted and the role of such interactions in many biological processes may yet to be uncovered.

Topology of RNA–protein nucleobase–amino acid π–π interactions and comparison to analogous DNA–protein π–π contacts

“…S2; Wilson et al 2014Wilson et al , 2015. In this previous study, 1765 contacts were identified in 672 X-ray crystal structures published prior to January 2, 2014 with a resolution better than 2.0 Å.…”

“…Due to the importance of nucleic acid-protein interactions, a number of studies have analyzed experimental Xray crystal structures to understand the types of atomic level interactions between DNA Luscombe and Thornton 2002;Gromiha et al 2004aGromiha et al ,b, 2005Mao et al 2004;Lejeune et al 2005;Prabakaran et al 2006;Baker and Grant 2007;Sathyapriya et al 2008;Wilson et al 2014Wilson et al , 2015 or RNA (Allers and Shamoo 2001;Jones et al 2001;Treger and Westhof 2001;Cheng et al 2003;Jeong et al 2003;Lejeune et al 2005;Morozova et al 2006;Baker and Grant 2007;Ellis et al 2007;Bahadur et al 2008;Barik et al 2015) nucleotides and amino acids that govern nucleic acid recognition and binding. These studies have determined that nucleic acid-protein contacts span hydrogen bonding (direct or water mediated), ionic (salt-bridge or phosphate backbone), van der Waals, and hydrophobic interactions.…”

“…Previous analyses of nucleic acid-protein crystal structures reveal small distances between the nucleobases and π-containing amino acids (Jones et al 2001;Luscombe et al 2001;Treger and Westhof 2001;Lejeune et al 2005;Morozova et al 2006;Baker and Grant 2007;Ellis et al 2007;Wilson et al 2014;Barik et al 2015;Wilson et al 2015). Indeed, despite the involvement of the DNA nucleobases in stable stacking interactions within the double helix, an abundance of nucleobase-amino acid π-interactions (π-contacts) have been identified in DNA-protein complexes Lejeune et al 2005;Baker and Grant 2007;Wilson et al 2014;Wilson et al 2015).…”

“…Indeed, despite the involvement of the DNA nucleobases in stable stacking interactions within the double helix, an abundance of nucleobase-amino acid π-interactions (π-contacts) have been identified in DNA-protein complexes Lejeune et al 2005;Baker and Grant 2007;Wilson et al 2014;Wilson et al 2015). Since most RNA nucleobases are not stacked within duplexes, nucleobase-amino acid π-interactions can occur without requiring unfavorable conformational changes and with the added benefit of sequestering the bases from solvent.…”

“…Besides the aromatic amino acids, Morozova et al (2006) and Barik et al (2015) both report significant involvement of R in nucleobase π-π stacking interactions. Furthermore, previous work has illustrated that other relative orientations of nucleobases and π-containing amino acids besides (planar) stacked arrangements (e.g., perpendicular T-shaped orientations) may also contribute significantly to the stability and function of nucleic acidprotein complexes (Rutledge et al 2009;Wilson et al 2014Wilson et al , 2015.…”