The polymorphism R441Q of the chicken WWP1 ubiquitin protein ligase affects its functional and structural proprieties: possible implications to genetic muscular dystrophy / O polimorfismo R441Q da enzima ligase WWP1 da proteína ubiquitina de galinha afeta suas propriedades funcionais e estruturais: possíveis implicações à distrofia muscular genética

• Autor(a) principal: Gabriel, Jane Eyre
• Data de Publicação: 2021
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Revista Veras
• DOI: 10.34117/bjdv7n1-725
• Texto Completo: https://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/23908
• topic: Bioinformatics; in silico prediction; muscular dystrophy; single nucleotide polymorphism; WWP1 protein.

The current study aimed to assess the effects of the causal polymorphism R441Q on the functional and structural proprieties of the WWP1 ubiquitin-protein ligase of chicken Gallus gallus by in silico prediction analyses. Amino acid sequences of chicken WWP1 were selected from database UniProtKB/Swiss-Prot: a) wild sequence (Q5F372) with arginine (R) at position 441, and b) mutant sequence harboring the polymorphism R441Q, substituting arginine by glutamine (Q) at same position. The WWP1 sequences were submitted as input to different Bioinformatics’ tools to investigate the functional impacts of this replacement on eventual alterations in their tridimensional structure modeling. Results showed that the polymorphism R441Q of the chicken mutant WWP1 was predicted as deleterious, and the predictive tridimensional model for mutant WWP1 demonstrated lower modeling quality with strongly negative scores than those generated for wild protein. Interestingly, preliminary experimental findings have showed that single nucleotide variants in the WWP1 gene are possibly enough to affect its biological function, provoking potential risks to muscular dystrophy in chickens. Thus, the findings described herein suggest that the replacement of the arginine by glutamine amino acids provoked local conformational changes in the R441Q-harboring WWP1 protein, which could directly affect its post-translational folding mechanisms and biological functionality, and consequently trigger the pathogenesis associated with genetic muscular dystrophy in chickens.