Caracterização in silico da DARPP-32 em seres humanos

Abstract

Introduction: PPPR1A, PPPR1B and PPPR1C are members of a protein family known for its inhibitory effect of protein phosphatase 1 (PP1). Among them, PPPR1B (DARPP-32) is the most studied. Some investigations relate these proteins, especially DARPP-32, to several human diseases such as cancer, schizophrenia and chemical dependence. In silico studies about these proteins are scarce and their threedimensional structure is still unknown. Justification: Understand the properties and function of a particular group of proteins, providing an understanding of their biochemistry, physiology and biological effects that may assist future studies on therapeutic alternatives against various diseases in which these proteins are involved. Goals: Evaluate the molecular biodiversity of DARPP-32 and its potential counterparts. a) Identify potential homologues of DARPP-32 in humans; b) Characterize their biochemical properties; c) Evaluate the protein architecture of selected molecular targets; d) Construct multiple sequence alignments; e) Identify patterns of conservation and divergence in these sequences. Methodology: a) Bibliographic survey; b) Searches in databases and bioinformatics tools; c) Search for sequences and identification of potential homologues; d) Evaluation of protein architecture; e) Classification of protein sequences; f) Biochemical characterization of proteins of interest; g) Construction of multiple sequence alignments. Results and Discussion: It has been identified some Potential homologues of DARPP-32. PPP1R1A, PPP1R1B and PPP1R1C share a domain (Pfam: PF05395) that determines their biochemical properties such as structural disorder and molecular interactions. Only PPP1R1B has a glutamate-rich region. The physicochemical properties were analyzed by identifying disorder sub-regions in these proteins. The results show that DARPP-32 and other members of this protein family are Intrinsically Disordered Proteins (PIDs) possessing potentially phosphorylated residues, especially in serine and threonine, and other post-translational modifications. Conclusion and Perspectives: This work will help understanding the structure and function of these proteins (especially DARPP-32), assisting research on the molecular evolution and therapies against diseases in which they are involved.