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Structural and functional studies of the Golgi Re-Assembly and Stacking Protein (GRASP) from Cryptococcus neoformans

Abstract

The incidence of highly lethal fungi infections has grown dramatically, making those infections a serious public health problem, especially when involving immunosupressed patients. The lack of specific treatments with high efficiency and low colateral effects make the search for understanding the fungi mechanisms of action an issue of great interest. Cryptococcus neoformans is one of the major fungi species in Brazil and that seems to be the only phatogenic species of Cryptococcus. The virulence of this pathogen is associated with the external capsule formed by several biomolecules produced in the intracellular space and that reach the extracellular space by means of non conventional secretion mechanisms. Although not fully understood, a common feature of those mechanisms is that they rely on the Golgi Re-assembly and stacking proteins (GRASPs). GRASPs have been associated with a series of roles not only in the structural organization of the Golgi, but also in non-conventional secretion. However, its precise role in those processes can still benefit from structural and functional result at a molecular level. This project aims at producing experimental data that will allow a structure-function correlation of the C. neoformans GRASP (CnGRASP). To achieve our goal, we will make use of a combination of experimental techniques in Molecular Biophysics that will cover aspects from the X-ray crystal structure of CnGRASP to the study of CnGRASP interaction with natural ligands, such as GXM, and with membrane model systems. (AU)

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Scientific publications (14)
(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)
KAVA, EMANUEL; MENDES, LUIS F. S.; BATISTA, MARIANA R. B.; COSTA-FILHO, ANTONIO J.. Myristoylation and its effects on the human Golgi Reassembly and Stacking Protein 55. Biophysical Chemistry, v. 279, . (15/50366-7, 16/16328-3, 17/24669-8, 12/20367-3)
MENDES, LUIS F. S.; FONTANA, NATALIA A.; OLIVEIRA, CAROLINA G.; FREIRE, MARJORIE C. L. C.; LOPES, JOSE L. S.; MELO, FERNANDO A.; COSTA-FILHO, ANTONIO J.. The GRASP domain in golgi reassembly and stacking proteins: differences and similarities between lower and higher Eukaryotes. FEBS Journal, v. 286, n. 17, p. 3340-3358, . (17/24669-8, 15/50366-7, 16/23863-2, 09/53989-4, 12/20367-3)
MENDES, LUIS FELIPE S.; BATISTA, MARIANA R. B.; JUDGE, PETER J.; WATTS, ANTHONY; REDFIELD, CHRISTINA; COSTA-FILHO, ANTONIO J.. Conformational flexibility of GRASPs and their constituent PDZ subdomains reveals structural basis of their promiscuous interactome. FEBS Journal, v. 287, n. 15, . (12/20367-3, 15/50366-7, 16/09676-5, 17/24669-8)
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, . (14/00206-0, 15/50366-7, 11/21767-2, 15/18390-5, 12/13309-7, 12/20367-3)
MICHELETTO, MARIANA C.; GUIDELLI, EDER J.; COSTA-FILHO, ANTONIO J.. Interaction of Genetically Encoded Photosensitizers with Scintillating Nanoparticles for X-ray Activated Photodynamic Therapy. ACS APPLIED MATERIALS & INTERFACES, v. 13, n. 2, p. 2289-2302, . (18/13016-6, 12/20367-3, 15/50366-7)
MENDES, LUIS F. S.; GARCIA, ASSUERO F.; KUMAGAI, PATRICIA S.; DE MORAIS, FABIO R.; MELO, FERNANDO A.; KMETZSCH, LIVIA; VAINSTEIN, MARILENE H.; RODRIGUES, MARCIO L.; COSTA-FILHO, ANTONIO J.. New structural insights into Golgi Reassembly and Stacking Protein (GRASP) in solution. SCIENTIFIC REPORTS, v. 6, . (12/13309-7, 12/20367-3)
REDDY, S. THIRUPATHI; UVERSKY, VLADIMIR N.; COSTA-FILHO, ANTONIO J.. Biophysical characterization of intrinsically disordered human Golgi matrix protein GRASP65. International Journal of Biological Macromolecules, v. 162, p. 1982-1993, . (15/50366-7, 17/12146-0, 15/16812-0, 12/20367-3)
REDDY, S. THIRUPATHI; UVERSKY, VLADIMIR N.; COSTA-FILHO, ANTONIO JOSE. Nucleation-dependent amyloid fibrillation of human GRASP55 in aqueous solution. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, v. 49, n. 2, p. 133-143, . (12/20367-3, 17/12146-0, 15/50366-7)
THIRUPATHI REDDY, S.; SANTOS MENDES, LUIS FELIPE; FONTANA, NATALIA APARECIDA; COSTA-FILHO, ANTONIO JOSE. Exploring structural aspects of the human Golgi matrix protein GRASP55 in solution. International Journal of Biological Macromolecules, v. 135, p. 481-489, . (16/23863-2, 17/12146-0, 17/24669-8, 15/16812-0, 15/50366-7, 12/20367-3)
BARROSO, RAFAEL P.; BASSO, LUIS G. M.; COSTA-FILHO, ANTONIO J.. Interactions of the antimalarial amodiaquine with lipid model membranes. Chemistry and Physics of Lipids, v. 186, p. 68-78, . (10/17662-8, 12/20367-3)
GARCIA, ASSUERO F.; LOPES, JOSE L. S.; COSTA-FILHO, ANTONIO J.; WALLACE, BONNIE A.; ARAUJO, ANA P. U.. Membrane Interactions of S100A12 (Calgranulin C). PLoS One, v. 8, n. 12, . (10/17662-8, 12/20367-3)
FONTANA, N. A.; FONSECA-MALDONADO, R.; MENDES, L. F. S.; MELEIRO, L. P.; COSTA-FILHO, A. J.. The yeast GRASP Grh1 displays a high polypeptide backbone mobility along with an amyloidogenic behavior. SCIENTIFIC REPORTS, v. 8, . (15/18390-5, 16/09676-5, 15/50366-7, 12/13309-7, 12/20367-3, 16/23863-2)
MENDES, LUIS F. S.; FONTANA, NATALIA A.; REDDY, S. THIRUPATHI; UVERSKY, VLADIMIR N.; COSTA-FILHO, ANTONIO J.. The exquisite structural biophysics of the Golgi Reassembly and Stacking Proteins. International Journal of Biological Macromolecules, v. 164, p. 3632-3644, . (12/20367-3, 15/50366-7, 16/23863-2, 17/24669-8, 17/12146-0)
MENDES, LUIS F. S.; BATISTA, MARIANA R. B.; KAVA, EMANUEL; BLEICHER, LUCAS; MICHELETTO, MARIANA C.; COSTA-FILHO, ANTONIO J.. Resurrecting Golgi proteins to grasp Golgi ribbon formation and self-association under stress. International Journal of Biological Macromolecules, v. 194, p. 264-275, . (16/16328-3, 15/16812-0, 15/50366-7, 12/20367-3, 18/13016-6, 17/24669-8)

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