Structure-function analysis of lipid binding proteins from parasitic helminthes

Team of work

Principal InvestigatorFranchini

Franchini, Gisela Raquel


Giorello, Alejandra N. Giorello

Research Fellow

Rodríguez, SantiagoRodriguez Santiago

Research Fellow

Lombardo, José Lombardo

Research Fellow

Sisti, Martín SebastiánSisti

Research Fellow

Arce, Lucas FedericoArce

Research Fellow

Collaborators from other institutions

Estévez, Adriana
Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

Ferreira, Ana M.
Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República (UdelaR), Montevideo, Uruguay.

Ferreyra, Henrique
Centro de Biotecnología and Departamento de Biología Molecular e Biotecnología, Universidad Federal do Rio Grande do Sul, Porto Alegre, Brasil.

Kennedy, Malcolm W.
Institute of Molecular, Cell and Systems Biology, Glasgow University, Glasgow, Escocia.

Smith, Brian O
Institute of Molecular, Cell and Systems Biology, Glasgow University, Glasgow, Escocia.

Zaha, Arnaldo
Centro de Biotecnología and Departamento de Biología Molecular e Biotecnología, Universidad Federal do Rio Grande do Sul, Porto Alegre, Brasil.

Costabel, Marcelo
DGrupo de Biofísica, Departamento de Física, Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina.

Radman, Nilda
Cátedra de Parasitología Comparada, Facultad de Cs. Veterinarias, UNLP, La Plata, Argentina.

Rosenzvit, Mara
Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Facultad de Medicina, (UBA-CONICET), Buenos Aires, Argentina.

Line overview

Helminth parasites produce and secrete a great variety of lipid binding proteins (LBPs) that are structurally distinct from those of their hosts. Cestodes and parasitic nematodes present a restricted lipid metabolism, sometimes lacking complete pathways required for the synthesis of fatty acids and sterols, and must acquire simple and complex lipids from their hosts. Although their specific function is still unknown, LBPs from parasites are thought to participate in the acquisition of lipids from their hosts. It is also postulated that LBPs might interfere in the regulation of the host´s immune response by sequestering signalling molecules.

The general aims of this line of investigation are dedicated to explore the structure and biophysical properties of these LBPs that are exclusively found in these organisms and are potentially involved in their survival. Knowing more about the structure of these proteins as well as their interactions with ligands and membranes, is important to understand host-parasite interactions that they could mediate. On the other hand, these studies will contribute with further knowledge about the mechanisms of helminth infection and the role that these proteins play in helminths biology. Moreover, this information would be useful in the establishment of new therapeutics and prevention of the diseases caused by these parasites.

We are currently working with four important types of LBPs from parasites with global and local epidemiological importance (Ascaris summ, A. lumbricoides, Necator americanus, Echinococcus granulosus):

a) Fatty acid and retinol binding proteins (FARs) with a structure that has no known counterpart and are exclusively found in nematodes.
b) Nematodes polyprotein allergens (NPAs) also unique to nematodes are synthesized as large precursors comprising tandemly repeated units that are cleaved posttranslationally into multiple ~15 kDa protein units.
c) Relatives of the Fatty Acid Binding Proteins (FABPs) family, found in both, cestodes and some structurally modified in ways that are unique to nematodes.
d) Antigen B, a member of a new family of hydrophobic ligand binding proteins (HLBPs) from cestodes.

Function of lipid binding proteins of parasitic helminths: still a long road.
Lombardo, Jose F.; Pórfido, Jorge L.; Sisti, Martín S.; Giorello, A. Nahili; Rodríguez, Santiago; Córsico, Betina; Franchini, Gisela R.
2022: Parasitology research. : SPRINGER, ISSN 0932-0113

LIDeB Tools: A Latin American resource of freely available, open-source cheminformatics apps.
Prada Gori, Denis N. ; Alberca, Lucas N.; Rodríguez, Santiago; Alice, Juan I.; Llanos, Manuel A.; Bellera, Carolina L.; Talevi, Alan.
2022. Artificial intelligence in the life sciences. Elsevier. vol. 2, p. 1-11. ISSN 2667-3185

A look into a wormy friend: The model of Caenorhabditis Elegans.
Jose Francisco Lombardo.
2021. Physiological mini-reviews: Argentinean Physiological Society and the Latin American Association of Physiological Sciences,- . vol. 14, n° 5, ISSN 1669-5402

Can drug repurposing strategies be the solution tothe COVID-19 crisis?
Carolina L. Bellera; Manuel A. Llanos; Melisa E. Gantner; Santiago Rodríguez; Luciana Gavernet; Marcelo Comini; Alan Talevi.
2020. Expert opinion on drug discovery. London: INFORMA HEALTHCARE, p. 1-8. ISSN 1746-0441

Fatty acid-binding proteins in Echinococcus spp.: the family has grown.
Pórfido, Jorge L.; Herz, Michaela; Kiss, Ferenc; Kamenetzky, Laura; Brehm, Klaus; Rosenzvit, Mara C.; Córsico, Betina; Franchini, Gisela R.
2020. Parasitology research. Berlin: SPRINGER, 2020 - . vol. 119, n° 4, p. 1401-1408. ISSN 0932-0113

Application of target repositioning and in silico screening to exploit Fatty Acid Binding Proteins (FABPs) from Echinococcus multilocularis as possible drug targets.
Belgamo J. A.; Alberca L. N.; Pórfido J. L; Caram Romero F.N.; Rodriguez S.; Talevi A.; Córsico B; Franchini G.
2020. Journal of computer-aided molecular design. SPRINGER. ISSN 0920-654X

Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode.
Ibáñez-Shimabukuro, Marina; Rey-Burusco, M. Florencia; Gabrielsen, Mads; Franchini, Gisela R.; Riboldi-Tunnicliffe, Alan; Roe, Andrew J.; Griffiths, Kate; Cooper, Alan; Córsico, Betina; Kennedy, Malcolm W.; Smith, Brian O.
2019: Bioscience reports. PORTLAND PRESS LTD, vol. 39, n° 7, ISSN 0144-8463

Dioctophyme renale in a domestic cat (Felis catus): Renal location and nephrectomy.
Butti, M. j; Gamboa, I; Terminiello, J. D; Franchini, G. R; Giorello, A. N; Maldonado, L. L; Kamenetzky, L; Luna, M- F; López Merlo, M.; Radman Nilda.
2019: Veterinary parasitology: regional studies and reports: Elsevier. vol. 18, ISSN 2405-9390

Fatty Acid and Retinol-Binding Protein: Unusual Protein Conformational and Cavity Changes Dictated by Ligand Fluctuations.
Barletta, G. P.; Franchini, G.; Córsico, B.; Fernández-Alberti, S.
2019: Journal of chemical information and modeling. Washington: AMER CHEMICAL SOC, vol. 59, n° 8, p. 3545-3555. ISSN 1549-9596

Identification and characterization of the major pseudocoelomic proteins of the giant kidney worm, Dioctophyma renale.
Giorello, N; Kennedy, M. W; Butti, M; Radman, N; Córsico, B; Franchini, G.
2017. Parasites and vectors. Londres: BIOMED CENTRAL LTD. ISSN 1756-3305

FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism.
Rodriguez Sawicki, L; Bottasso Arias, N. M; Scaglia, N; Falomir Lockhart, L; Franchini, G. R; Storch, J; Córsico, B.
2017. Biochimica et biophysica acta-molecular and cell biology of lipids. ELSEVIER SCIENCE BV. vol. 1862, n° 12, p. 1587-1594. ISSN 1388-1981

Analysis of triglyceride synthesis unveils a green algal soluble diacylglycerol acyltransferase and provides clues to potential enzymatic components of the chloroplast pathway.
Bagnato, C; Prados, M. B; Franchini, G. R; Scaglia, N; Miranda, S. E; Beligni, M. V.
2017. Bmc genomics: BIOMED CENTRAL LTD. vol. 18, n° 1, ISSN 1471-2164

Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cellresponse to inflammation. Parasites and vectors.
Silva, V; Folle, A; Ramos. A; Kitano, E; Iwai, L; Corraliza, I; Córsico, B; Ferreira, A.
2016. Londres: BIOMED CENTRAL LTD, vol. 9, n° 69, p. 1350-1357. ISSN 1756-3305

Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus.
Rey, M. F; Ibañez Shimabukuro, M; Gabrielsen, M; Franchini, G. R; Aj, R; Griffiths, K; Zhan, B; Cooper, A; Kennedy, M. W; Córsico, B; Smith, B. O.
2015. Biochemical Journal, Londres: PORTLAND PRESS LTD, vol. 471, p. 403-414. ISSN 0264-6021

Lipid-free antigen B subunits from Echinococcus granulosus: oligomerization, ligand binding, and membrane interaction properties.
Silva-Álvarez, V; Franchini, G. R; Pórfido, J. L; Kennedy, M. W; Ferreira, A. M; Córsico, B.
2015. PLoS Negl Trop Dis. 9(3): e0003552, doi: 10.1371/journal.pntd.0003552

Echinococcus granulosus antigen B: a Hydrophobic Ligand Binding Protein at the host-parasite interface.
Silva-Álvarez, V; Folle, A. M; Ramos, A. L; Zamarreño, F; Costabel, M. D; García-Zepeda, E; Salinas, G; Córsico, B; Ferreira, A. M.
2015.Prostaglandins Leukot Essent Fatty Acids. 93: 17-23, doi: 10.1016/j.plefa. 2014.09.008

Characterization of fatty acid binding and transfer from Δ98Δ, a functional all-β abridged form of IFABP.
Rodriguez Sawicki, L; Guerbi, M. X; Falomir Lockhart, L. J; Curto, L; Delfino, J.M; Córsico, B; Franchini, G. R.
2014. Biochimica et Biophysica acta-molecular and cell biology of lipids., Amsterdam: ELSEVIER SCIENCE BV, vol. 1841, p. 1733-1740. ISSN 1388-1981

IFABP portal region insertion during membrane interaction depends on phospholipid composition.
De Gerónimo, E; Rodriguez Sawicki, L; Bottasso, N; Franchini, G. R; Zamarreño, F; Costabel, M. D; Córsico, B; Falomir.Lockhart, L. J.
2014. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids., Amsterdam: ELSEVIER SCIENCE BV, 2014 - vol. 1841, p. 141-150. ISSN 1388-1981

The unusual lipid binding proteins of parasitic helminths and their potential roles in parasitism and as therapeutic targets.
Franchini, G. R; Porfido, J; Ibañez Shimabukuro, M; Rey Burusco, F; Belgamo, J; Smith, B. O; Kennedy, M. W; Córsico, B.
2014. Prostaglandins Leukotrienes and Essential Fatty Acids. Amsterdam: ELSEVIER SCI LTD,. vol. 1841, p. 1733-1740. ISSN 0952-3278

Resonance assignment of As-p18, a fatty acid binding protein secreted by developing larvae of the parasitic nematode Ascaris suum.
Ibáñez-Shimabukuro, M; Rey-Burusco, M. F; Cooper, A; Kennedy, M. W; Córsico, B; Smith, B. O.
2014. Biomol NMR Assign. 8(1): 33-6, 2014. doi: 10.1007/s12104-012-9447-1

¹H, ¹³C and ¹⁵N chemical shift assignments of Na-FAR-1, a helix-rich fatty acid and retinol binding protein of the parasitic nematode Necator americanus.
Rey-Burusco, M. F; Ibañez-Shimabukuro, M; Cooper, A; Kennedy, M. W; Córsico, B; Smith, B. O.
2014. Biomol NMR Assign. 8(1): 19-21, doi: 10.1007/s12104-012-9444-4

Useable diffraction data from a multiple microdomain-containing crystal of Ascaris suum As-p18 fatty-acid-binding protein using a microfocus beamline.
Gabrielsen, M; Riboldi-Tunnicliffe, A; Ibáñez-Shimabukuro, M; Griffiths, K; Roe, A. J; Cooper, A; Smith, B. O; Córsico, B; Kennedy, M. W.
2012. Acta Crystallogr Sect F Struct Biol Cryst Commun. 68(Pt 8): 939-41, doi: 10.1107/S1744309112026553

Two crystal forms of a helix-rich fatty acid- and retinol-binding protein, Na-FAR-1, from the parasitic nematode Necator americanus.
Gabrielsen, M; Rey-Burusco, M. F; Griffiths, K; Roe, A. J; Cooper, A; Smith, B. O; Kennedy, M. W; Corsico, B.
2012. Acta Crystallogr Sect F Struct Biol Cryst Commun. 68(Pt 7): 835-8, doi: 10.1107/S1744309112023597

Direct interaction between EgFABP1, a fatty acid binding protein from Echinococcus granulosus, and phospholipid membranes.
Porfido, J. L; Alvite, G; Silva, V; Kennedy, M. W; Estevez, A; Corsico, B.
2012. PLoS Negl Trop Dis. 6(11): e1893, doi: 10.1371/journal.pntd.0001893

Structure-Based Binding Pocket Detection and Druggability Assessment.
Rodríguez, Santiago; Alice, Juan I.; Bellera, Carolina L.; Talevi, Alan.
2022. Springer, p. 83-97. ISBN 978-3-030-95894-7
DOI: 10.1007/978-3-030-95895-4_5

Análisis estructural y funcional de macromoléculas.
Córsico, B; Falomir-Lockhart, L. J; Franchini, G. R; Scaglia, N.
2013. La Plata. Libro de Catedra. Edulp, p. 422. ISBN 978-950-34-1057-8

Microscopía Óptica.
Falomir Lockhart, L. J; Fuentes, F; Córsico, B; Franchini, G. R; Scaglia, N.
2013. Capítulo 13. Microscopía Óptica. La Plata: EDULP, 2013. p. 365-416. ISBN 978-950-34-1057-8

De Gerónimo, E; Falomir Lockhart, L. J; Córsico, B; Franchini, Gr; Scaglia, N.
2013. Capítulo 2. Fluorescencia. La Plata: EDULP, 2013. p. 39-77. ISBN 978-950-34-1057-8

Interaccion Proteina Proteina.
Rodriguez Sawicki, L; Bottasso, N; Córsico, B; Franchini, G; Falomir Lockhart, L. J; Scaglia, N.
2013. La Plata: EDULP, 2013. p. 299-342

Unique functions of Intestinal FABPs.
Corsico, B; Storch, J.
2009. Fatty Acid Binding Proteins. Transworld Research Network, p. 128-140. ISBN 978-81-7895-410-3

“Premio mejor trabajo”
Academia Nacional de Farmacia y Bioquímica. Jornadas de la Sección Bioquímica de la Academia. Herramientas Modernas para el Estudio de Aspectos Estructurales de Proteínas”. 2009. Structural and biophysical analysis of novel lipid binding proteins from parasitic helminths.
Ibañez, M; Rey F; Pórfido, J; Silva, V; Franchini, G. R; Córsico, B.

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