Molecular recognition in septins: the interface studies between SEPT7 and SEPT12

• Grant number: 16/19734-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2017
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Richard Charles Garratt
• Grantee: Danielle Karoline Silva Do Vale Castro
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 14/15546-1 - Septins: comparative studies and the correlation between structure and function, AP.TEM

Abstract

Septins belong to a large family of proteins characterized by a conserved GTP-binding domain. First identified in yeast, about 40 years ago, in which play an important role in septation and cell division, these proteins are associated with diverse cellular processes and various pathologies in eukaryotes. For these reasons it is essential to understand the molecular and physiological basis of their functions and the role of GTP binding and hydrolysis. Currently, one of the greatest challenges in septin biochemistry is to understand their ability to self-assemble into heterofilamentos and the subsequent organization of these filaments into higher order structures. This aspect is fundamental to our understanding of their biochemistry as well as to better elucidate their possible role in different pathologies. This proposal aims to undertake structural and biophysical studies of the interaction between the G-domains (GTP-binding domains) of SEPT7 and SEPT12, which has yet to be studied in structural terms. As a starting point, the main target for crystallization trials and structure determination is the heterodimer, whose existence in vivo has already been reported in the literature. Additionally, based on mutations found in the SEPT12 protein (SEPT12T89M and SEPT12D197N) in infertile men, a comparative analyzes of the native and mutant proteins in terms of their interaction with SEPT7 will be undertaken, in order to assess the role of the specific residues involved. The results of this work will contribute effectively to advance our understanding of the formation of filaments that make up the annulus of the spermatozoid and how they are associated with the phenotypes presented in infertile men. (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)

SILVA DO VALE CASTRO, DANIELLE KAROLINE; DE OLIVEIRA DA SILVA, SABRINA MATOS; PEREIRA, HUMBERTO D'MUNIZ; ALVES MACEDO, JOCI NEUBY; LEONARDO, DIEGO ANTONIO; VALADARES, NAPOLEAO FONSECA; KUMAGAI, PATRICIA SUEMY; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface. IUCRJ, v. 7, n. 3, p. 462-479, MAY 2020. (10/20290-5, 16/19734-2, 16/04658-9, 12/00268-0, 14/15546-1)

SILVA DO VALE CASTRO, DANIELLE KAROLINE; DE OLIVEIRA DA SILVA, SABRINA MATOS; PEREIRA, HUMBERTO D'MUNIZ; ALVES MACEDO, JOCI NEUBY; LEONARDO, DIEGO ANTONIO; VALADARES, NAPOLEAO FONSECA; KUMAGAI, PATRICIA SUEMY; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface. IUCRJ, v. 7, p. 18-pg., 2020-05-01. (16/04658-9, 16/19734-2, 14/15546-1, 10/20290-5, 12/00268-0)

Academic Publications

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

CASTRO, Danielle Karoline Silva Do Vale. Molecular recognition in septins: the interface studies between SEPT7 and SEPT12. 2018. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT) São Carlos.