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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 10
[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
Total Affiliations: 5
Document type: Journal article
Source: Journal of Biological Chemistry; v. 289, n. 11, p. 7799-7811, MAR 14 2014.
Web of Science Citations: 16

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