Crystal Structure of a Schistosoma mansoni Septin Reveals the Phenomenon of Strand Slippage in Septins Dependent on the Nature of the Bound Nucleotide

Author(s)

Zeraik, Ana E. ^[1] ; Pereira, Humberto M. ^[1] ; Santos, Yuri V. ^[1] ; Brandao-Neto, Jose ^[2] ; Spoerner, Michael ^[3] ; Santos, Maiara S. ^{[4, 5]} ; Colnago, Luiz A. ^[5] ; Garratt, Richard C. ^[1] ; Araujo, Ana P. U. ^[1] ; DeMarco, Ricardo ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13563120 Sao Carlos, SP - Brazil

^[2] Diamond Light Source, Didcot OX11 0DE, Oxon - England

^[3] Univ Regensburg, Ctr Magnet Resonance Chem & Biomed, Inst Biophys & Phys Biochem, D-93053 Regensburg - Germany

^[4] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[5] Embrapa Instrumentacao, BR-13560970 Sao Carlos, SP - Brazil

• Document type: Journal article
• Source: Journal of Biological Chemistry; v. 289, n. 11, p. 7799-7811, MAR 14 2014.
• Web of Science Citations: 16

Abstract

Background: Septins are filament-forming proteins involved in membrane-remodeling events. Results: Two crystal structures of a septin with the highest resolution to date reveal the phenomenon of -strand slippage. Conclusion: A novel mechanistic framework for the influence of the nature of the bound nucleotide and the presence of Mg2+ in septins is proposed. Significance: Identification of strand slippage might contribute to elucidating the mechanism of septin association with membranes. Septins are filament-forming GTP-binding proteins involved in important cellular events, such as cytokinesis, barrier formation, and membrane remodeling. Here, we present two crystal structures of the GTPase domain of a Schistosoma mansoni septin (SmSEPT10), one bound to GDP and the other to GTP. The structures have been solved at an unprecedented resolution for septins (1.93 and 2.1 , respectively), which has allowed for unambiguous structural assignment of regions previously poorly defined. Consequently, we provide a reliable model for functional interpretation and a solid foundation for future structural studies. Upon comparing the two complexes, we observe for the first time the phenomenon of a strand slippage in septins. Such slippage generates a front-back communication mechanism between the G and NC interfaces. These data provide a novel mechanistic framework for the influence of nucleotide binding to the GTPase domain, opening new possibilities for the study of the dynamics of septin filaments. (AU)

• FAPESP's process: 08/57910-0 - National Institute of Structural Biotechnology and Medicinal Chemistry in Infectious Diseases
• Grantee: Richard Charles Garratt
• Support type: Research Projects - Thematic Grants