In silico prediction of the functional and structural consequences of the non-synonymous single nucleotide polymorphism A122V in bovine CXC chemokine receptor type 1

Abstract

<jats:p>Abstract The current study aimed to assess whether the A122V causal polymorphism promotes alterations in the functional and structural proprieties of the CXC chemokine receptor type 1 protein (CXCR1) of cattle Bos taurus by in silico analyses. Two amino acid sequences of bovine CXCR1 was selected from database UniProtKB/Swiss-Prot: a) non-polymorphic sequence (A7KWG0) with alanine (A) at position 122, and b) polymorphic sequence harboring the A122V polymorphism, substituting alanine by valine (V) at same position. CXCR1 sequences were submitted as input to different Bioinformatics’ tools to examine the effects of this polymorphism on functional and structural stabilities, to predict eventual alterations in the 3-D structural modeling, and to estimate the quality and accuracy of the predictive models. The A122V polymorphism exerted tolerable and non-deleterious effects on the polymorphic CXCR1, and the predictive structural model for polymorphic CXCR1 revealed an alpha helix spatial structure typical of a receptor transmembrane polypeptide. Although higher variations in the distances between pairs of amino acid residues at target-positions are detected in the polymorphic CXCR1 protein, more than 97% of the amino acid residues in both models were located in favored and allowed conformational regions in Ramachandran plots. Evidences has supported that the A122V polymorphism in the CXCR1 protein is associated with increased clinical mastitis incidence in dairy cows. Thus, the findings described herein prove that the replacement of the alanine by valine amino acids provokes local conformational changes in the A122V-harboring CXCR1 protein, which could directly affect its post-translational folding mechanisms and biological functionality.</jats:p>

In Silico Tools for Analysis of Single-Nucleotide Polymorphisms in the Bovine Transferrin Gene

“…The same study identified 14 variants as deleterious using the PROVEAN tool, while SIFT identified 15 variants that affected the protein function, and I-Mutant found 16 variants that were deleterious and were efficient in destabilizing proteins [30]. In another in silico study with an A122V substitution, the effect on the bovine CXCR1 protein was determined, and it was found to have a tolerable (SIFT), (PolyPhen-2) and nondeleterious (I-Mutant) effect [37].…”

Molecular transduction in receptor-ligand systems by planar electromagnetic fields

“…The effects of amino acid mutations have been the subject of wide-ranging research (Guzzi et al, 2020). In the action of calcium pumps, a number of studies have shown that on mutating the R560 residue (whose position is considered to be strategic), the functionality of the pumps is altered.…”