Molecular interactions in the mechanism of action of human galectin-4

• Grant number: 11/21767-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2012
• End date: March 31, 2016
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Antonio José da Costa Filho
• Grantee: Patricia Suemy Kumagai
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated scholarship(s): 12/20358-4 - Molecular interactions in the mechanism of action of P7 protein from the Hepatitis C virus and of human galectin 4, BE.EP.DD

Abstract

The family of galectins comprise a group of lectins whose Carbohydrate Recognition Domains (CRDs) have affinity for ²-galactosides. These are widely distributed in normal and neoplastic cells of different organisms and are involved in a wide variety of cellular events. The galectins have been the focus of recent studies mainly for their involvement in various cellular processes such as inflammation, cancer, cell adhesion, tumor progression and metastasis. However, many questions about their interactions with different carbohydrates, the specificity of these interactions and the specific role of galectins remain unanswered. In several of these functions, galectins pass through one or more stages of interaction with molecules present in cell membranes. In this study, we propose the investigation of carbohydrate-dependent interactions of human galectin-4 (Hgal-4) and its Carbohydrate Recognition Domains (CRD CRD-I and-II) through a set of biophysical methods. These interactions involve these proteins with their possible functional ligands which are biological membranes and various carbohydrates. The methodology involves a set of experimental methods consisting of electronic and nuclear magnetic resonance, circular dichroism, fluorescence and calorimetry. In addition, interaction studies, localization of Hgal-4 and co-localization of galectin in membrane phospholipids with the use of human cancer cell lines can be key models in the elucidation of their biological properties. Thus, two cell lines of colorectal cancer (HT-29 and HCT-116, over and down expression of endogenous Hgal-4, respectively) were selected for this purpose. The analysis of the results expected in this project in light of the structural data already available for the areas that make up the Hgal-4 may help to understand which molecular determinants responsible for protein-membrane interactions and thus correlate conformational changes of the domains and protein with full biological functions of Hgal-4. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RUSTIGUEL, JOANE K.; KUMAGAI, PATRICIA S.; DIAS-BARUFFI, MARCELO; COSTA-FILHO, ANTONIO J.; NONATO, MARIA CRISTINA. Recombinant expression, purification and preliminary biophysical and structural studies of C-terminal carbohydrate recognition domain from human galectin-4. Protein Expression and Purification, v. 118, p. 39-48, FEB 2016. (11/21811-1, 11/21767-2, 10/17662-8, 10/16153-2)

DIJKMAN, PATRICIA M.; MUNOZ-GARCIA, JUAN C.; LAVINGTON, STEVEN R.; KUMAGAI, PATRICIA SUEMY; DOS REIS, I, ROSANA; YIN, DANIEL; STANSFELD, PHILLIP J.; COSTA-FILHO, ANTONIO JOSE; WATTS, ANTHONY. Conformational dynamics of a G protein-coupled receptor helix 8 in lipid membranes. SCIENCE ADVANCES, v. 6, n. 33, AUG 2020. (10/17662-8, 12/20358-4, 11/21767-2)

MENDES, LUIS F. S.; BASSO, LUIS G. M.; KUMAGAI, PATRICIA S.; FONSECA-MALDONADO, RAQUEL; COSTA-FILHO, ANTONIO J.. Disorder-to-order transitions in the molten globule-like Golgi Reassembly and Stacking Protein. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1862, n. 4, p. 855-865, APR 2018. (12/20367-3, 12/13309-7, 15/50366-7, 11/21767-2, 14/00206-0, 15/18390-5)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

KUMAGAI, Patricia Suemy. Molecular interactions on mechanism action of human galectin-4. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.