Factors affecting the amplitude of the τ angle in proteins: a revisitation

Abstract

The protein folded state is the result of the fine balance of a variety of different forces. Even minor structural perturbations may have a significant impact on the stability of these macromolecules. Studies carried out in recent decades have led to the convergent view that proteins are endowed with a flexible spine. One of the open issues related to protein local backbone geometry is the identification of the factors that influence the amplitude of the τ (N-C-C) angle. Here, statistical analyses performed on an updated ensemble of X-ray protein structures by dissecting the contribution of the major factors that can potentially influence the local backbone geometry of proteins are reported. The data clearly indicate that the local backbone conformation has a prominent impact on the modulation of the τ angle. Therefore, a proper assessment of the impact of the other potential factors can only be appropriately evaluated when small (ϕ, ψ) regions are considered. Here, it is shown that when the contribution of the backbone conformation is removed by considering small (ϕ, ψ) areas, an impact of secondary structure, as defined by DSSP, and/or the residue type on τ is still detectable, although to a limited extent. Indeed, distinct τ-value distributions are detected for Pro/Gly and β-branched (Ile/Val) residues. The key role of the local backbone conformation highlighted here supports the use of variable local backbone geometry in protein refinement protocols.

Loop size optimization induces a strong thermal stabilization of the thioredoxin fold

“…The stereochemistry indicators of the refined model are in line with those displayed by well-refined structures as highlighted by the program PROCHECK [43]. The overall quality of the structure was also assessed by analyzing the variability in some geometrical parameters of the protein backbone [44][45][46][47]. Despite the rather low resolution of the structure, the final model is able to reproduce the variability in some backbone bond angles (NC a C, C b C a C, C a CO, C a CN +1 , and C -1 NC a ) and the deviation from planarity of the peptide bond (Dx) as function of conformation ( Fig.…”

Development of a Protein Scaffold for Arginine Sensing Generated through the Dissection of the Arginine-Binding Protein from Thermotoga maritima

“…Finally, to evaluate the accuracy of bond and dihedral angles of the final model, we checked the variability of the backbone valence angles and of the peptide planarity as a function of the local conformation. As shown in Table S1 and Figure S6 , the variability of these parameters follows the trends detected in highly accurate protein structures [ 45 , 46 , 47 ]. The atomic coordinates of D1 F57W have been deposited in the PDB with the identification code 7A99.…”

“…The final model presents R-factor and R-free values of 0.178 and 0.233, respectively. The stereochemistry of the final model was checked by using standard validation protocols such as PDB validator ( ) and Molprobity [ 44 ] and innovative approaches that are based on the evaluation of the conformation-dependent variability of the peptide geometry ( ) [ 45 , 46 , 47 ]. The analysis of the final model carried out with the Molprobity server indicates that it is endowed with a good stereochemistry ( Table 1 ).…”

The non-swapped monomeric structure of the arginine-binding protein from Thermotoga maritima

“…In particular, we looked for correlations between geometrical parameters and the local conformations of residues that are typically detected in highly accurate protein structures. Specifically, we checked the dependence on the angle (i) of the N-C -C bond angle (Karplus, 1996), (ii) of peptide-bond planarity and (iii) of the carbon carbonyl pyramidalization J C (Esposito et al, 2000(Esposito et al, , 2013Karplus, 1996;Improta et al, 2011;Balasco et al, 2017). As shown in Supplementary Fig.…”