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Biophysical studies of the structure-function correlation of TNAP in interaction with membrane models

Grant number: 18/12092-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2018
Effective date (End): October 31, 2020
Field of knowledge:Biological Sciences - Biophysics
Principal Investigator:Antonio José da Costa Filho
Grantee:Bruno Zoccaratto Favarin
Home Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Alkaline phosphatases are enzymes that catalyze the hydrolysis ofphosphomonoesters, thus producing phosphate and alcohol. These enzymes are dimers insolution and are found in the great majority of organisms. In humans, four alkalinephosphatases have been identified so far. Three of them are tissue-nonspecific alkalinephosphatases (TNAP) and can be expressed in any tissue in the body. In mammals, thisenzyme is associated with a genetic disorder that can lead to different levels of failure of thebone and blood vessel mineralization. The mechanisms used by TNAPs to perform theirfunctions are still not completely understood, but it is believed that TNAPs somehowcontribute to the increase of organic phosphate concentrations, promote bone mineralization,decreases concentration of extracellular phosphate, amongst others. TNAP is localized at theexternal part of the plasma membrane by means of a GPI (glycosylphosphatidylinositol)anchor. It is also frequently found associated with lipid rafts. Due to its biological relevance,TNAP has attracted attention of scientists from areas ranging from public health to basicScience, such as molecular biophysics. In this context, we propose in this project to use ourexpertise in the field of molecular biology and molecular biophysics to address the effects oflipid composition in the anchoring mechanism of TNAP as well as the effects of membranemodels in the catalytic activity. To do so we will make use of a combined experimentalapproach that will provide new insights about the TNAP structural features and its actionmechanism, thus advancing the knowledge in the field and with potential impact on bothbasic Science and public health.