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Structure and function of SARS-CoV spike glycoprotein fusion peptides

Grant number: 14/00206-0
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2014
Effective date (End): June 30, 2019
Field of knowledge:Physical Sciences and Mathematics - Physics - Condensed Matter Physics
Principal Investigator:Antonio José da Costa Filho
Grantee:Luís Guilherme Mansor Basso
Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):16/24452-6 - Structure determination of SARS fusion peptides by solid-state nuclear magnetic resonance spectroscopy, BE.EP.PD


The S2 domain of the spike (S) glycoprotein from Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV) is directly responsible for driving viral and host cell membrane fusion. Fusion peptides (FP), relatively hydrophobic segments located near the S2 domain N-terminus, play a crucial role in the fusion process. Although much information has been obtained in recent years on membrane fusion, many aspects of the molecular mechanism behind virus-host cell membrane fusion are not totally understood yet. In particular, many questions concerning the exact location and sequence of coronavirus fusion peptides as well as regarding the structure, dynamics, and topology of these molecules in lipid membranes still remain to be answered. In this project, we intend therefore to employ a wide variety of experimental and computational techniques to address these questions from different perspectives. Particularly, we are interested in a comparative structural and functional study of three membranotropic sequences, originally suggested as the putative fusion peptides of SARS-CoV S protein, and its corresponding non-fusogenic mutants to understand the role of each segment to the fusion reaction. It is also our interest to obtain a complete thermodynamic characterization of the interaction of the wild type peptides and their respective mutants with model membranes. Such information may also be determined via advanced molecular dynamics techniques, in which the free energy of binding, insertion, and peptide folding into lipid bilayers can be obtained. Knowledge of the structure and topology of these important membrane protein segments as well as the nature of the phospholipids-membrane peptides interactions are important to elucidate some of the steps of the complex and orchestrated membrane fusion mechanism mediated by viral glycoproteins. Additionally, besides being relevant to the stabilization and oligomerization of the S2 subunit, the transmembrane domain of the SARS-CoV S protein also plays an essential role in the fusion process. However, no structural explanation has been provided yet to elucidate the precise function of this domain. So, the additional purpose of this research proposal is to determine the structure, orientation, and oligomeric state of this peptide segment embedded into lipid model membranes. Thus, we aim to map out all the relevant regions of the S protein for the membrane fusion process at a molecular level, thereby building a detailed and comprehensive description of that phenomenon.

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Scientific publications (12)
(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)
SCORTECCI, JESSICA F.; SERRAO, VITOR HUGO B.; FERNANDES, ADRIANO F.; BASSO, LUIS G. M.; GUTIERREZ, RAISSA F.; ARAUJO, ANA PAULA U.; NETO, MARIO O.; THIEMANN, OTAVIO H.. Initial steps in selenocysteine biosynthesis: The interaction between selenocysteine lyase and selenophosphate synthetase. International Journal of Biological Macromolecules, v. 156, p. 18-26, . (12/23730-1, 16/20977-7, 14/00206-0, 13/17791-0, 14/16005-4)
VICENTE, EDUARDO F.; SAHU, INDRA D.; CRUSCA, JR., EDSON; BASSO, LUIS G. M.; MUNTE, CLAUDIA E.; COSTA-FILHO, ANTONIO J.; LORIGAN, GARY A.; CILLI, EDUARDO M.. HsDHODH Microdomain-Membrane Interactions Influenced by the Lipid Composition. Journal of Physical Chemistry B, v. 121, n. 49, p. 11085-11095, . (10/12953-4, 14/00206-0, 10/06526-6, 15/18390-5)
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, . (12/20367-3, 12/13309-7, 15/50366-7, 11/21767-2, 14/00206-0, 15/18390-5)
CRUSCA, JR., EDSON; MANSOR BASSO, LUIS GUILHERME; ALTEI, WANESSA FERNANDA; MARCHETTO, REINALDO. Biophysical characterization and antitumor activity of synthetic Pantinin peptides from scorpion's venom. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1860, n. 11, p. 2155-2165, . (14/18747-8, 14/00206-0)
SASTRE, DIEGO E.; BASSO, LUIS G. M.; TRASTOY, BEATRIZ; CIFUENTE, JAVIER O.; CONTRERAS, XABIER; GUEIROS-FILHO, FREDERICO; DE MENDOZA, DIEGO; NAVARRO, MARCOS V. A. S.; GUERIN, MARCELO E.. Membrane fluidity adjusts the insertion of the transacylase PlsX to regulate phospholipid biosynthesis in Gram-positive bacteria. Journal of Biological Chemistry, v. 295, n. 7, p. 2136-2147, . (16/05203-5, 15/21583-0, 14/00206-0, 14/13411-1)
SASTRE, DIEGO E.; PULSCHEN, ANDRE A.; BASSO, LUIS G. M.; PARIENTE, JHONATHAN S. BENITES; MARQUES NETTO, CATERINA G. C.; MACHINANDIARENA, FEDERICO; ALBANESI, DANIELA; NAVARRO, MARCOS V. A. S.; DE MENDOZA, DIEGO; GUEIROS-FILHO, FREDERICO J.. The phosphatidic acid pathway enzyme PlsX plays both catalytic and channeling roles in bacterial phospholipid synthesis. Journal of Biological Chemistry, v. 295, n. 7, p. 2148-2159, . (16/05203-5, 15/21583-0, 14/00206-0, 14/13411-1)
BASSO, LUIS G. M.; VICENTE, EDUARDO F.; CRUSCA, JR., EDSON; CILLI, EDUARDO M.; COSTA-FILHO, ANTONIO J.. SARS-CoV fusion peptides induce membrane surface ordering and curvature. SCIENTIFIC REPORTS, v. 6, . (10/12953-4, 09/10997-7, 08/57910-0, 14/00206-0, 15/18390-5)
MICHELETTO, MARIANA C.; MENDES, LUIS F. S.; BASSO, LUIS G. M.; FONSECA-MALDONADO, RAQUEL G.; COSTA-FILHO, ANTONIO J.. Lipid membranes and acyl-CoA esters promote opposing effects on acyl-CoA binding protein structure and stability. International Journal of Biological Macromolecules, v. 102, p. 284-293, . (12/13309-7, 15/50366-7, 14/00206-0, 15/18390-5)
VIEIRA, ERNANNI D.; BASSO, LUIS G. M.; COSTA-FILHO, ANTONIO J.. Non-linear van't Hoff behavior in pulmonary surfactant model membranes. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1859, n. 6, p. 1133-1143, . (10/17662-8, 14/00206-0, 15/18390-5)
FELIZATTI, ANA P.; ZERAIK, ANA E.; BASSO, LUIS G. M.; KUMAGAI, PATRICIA S.; LOPES, JOSE L. S.; WALLACE, B. A.; ARAUJO, ANA P. U.; DEMARCO, RICARDO. Interactions of amphipathic alpha-helical MEG proteins from Schistosoma mansoni with membranes. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1862, n. 3, . (14/09361-9, 14/00206-0, 18/19546-7, 15/50347-2)
MANSOR BASSO, LUIS GUILHERME; ZERAIK, ANA ELIZA; FELIZATTI, ANA PAULA; COSTA-FILHO, ANTONIO JOSE. Membranotropic and biological activities of the membrane fusion peptides from SARS-CoV spike glycoprotein: The importance of the complete internal fusion peptide domain. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1863, n. 11, . (08/57910-0, 15/50366-7, 14/00206-0, 15/18390-5)
BALASCO SERRAO, VITOR HUGO; DE FREITAS FERNANDES, ADRIANO; MANSOR BASSO, LUIS GUILHERME; SCORTECCI, JESSICA FERNANDES; CRUSCA JUNIOR, EDSON; LOPES CORNELIO, MARINONIO; MONSON DE SOUZA, BIBIANA; PALMA, MARIO SERGIO; DE OLIVEIRA NETO, MARIO; THIEMANN, OTAVIO HENRIQUE. The Specific Elongation Factor to Selenocysteine Incorporation in Escherichia coli: Unique tRNA(Sec) Recognition and its Interactions. Journal of Molecular Biology, v. 433, n. 23, . (13/17791-0, 14/00206-0, 12/15777-8, 12/23730-1, 14/16005-4, 98/14138-2)

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