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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.)

A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface

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Silva do Vale Castro, Danielle Karoline [1, 2] ; de Oliveira da Silva, Sabrina Matos [1, 2] ; Pereira, Humberto D'Muniz [1] ; Alves Macedo, Joci Neuby [1, 3] ; Leonardo, Diego Antonio [1] ; Valadares, Napoleao Fonseca [4] ; Kumagai, Patricia Suemy [1] ; Brandao-Neto, Jose [5] ; Ulian Araujo, Ana Paula [1] ; Garratt, Richard Charles [1]
Total Authors: 10
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Ave Joao Dagnone 1100, Sao Carlos 13563723, SP - Brazil
[2] Univ Sao Paulo, Inst Quim Sao Carlos, Ave Trabalhador Sao Carlense 400, Sao Carlos 13566590, SP - Brazil
[3] Fed Inst Educ Sci & Technol Rondonia, Rodovia BR 174, Km 3, Vilhena 76980000, RO - Brazil
[4] Univ Brasilia, Inst Ciencias Biol, Dept Biol Celular, Brasilia 70910900, DF - Brazil
[5] Harwell Sci & Innovat Campus, Diamond Light Source, Diamond House, Didcot OX11 0DE, Oxon - England
Total Affiliations: 5
Document type: Journal article
Source: IUCRJ; v. 7, n. 3, p. 462-479, MAY 2020.
Web of Science Citations: 0

Human septins 3, 9 and 12 are the only members of a specific subgroup of septins that display several unusual features, including the absence of a C-terminal coiled coil. This particular subgroup (the SEPT3 septins) are present in rod-like octameric protofilaments but are lacking in similar hexameric assemblies, which only contain representatives of the three remaining subgroups. Both hexamers and octamers can self-assemble into mixed filaments by end-to-end association, implying that the SEPT3 septins may facilitate polymerization but not necessarily function. These filaments frequently associate into higher order complexes which associate with biological membranes, triggering a wide range of cellular events. In the present work, a complete compendium of crystal structures for the GTP-binding domains of all of the SEPT3 subgroup members when bound to either GDP or to a GTP analogue is provided. The structures reveal a unique degree of plasticity at one of the filamentous interfaces (dubbed NC). Specifically, structures of the GDP and GTP gamma S complexes of SEPT9 reveal a squeezing mechanism at the NC interface which would expel a polybasic region from its binding site and render it free to interact with negatively charged membranes. On the other hand, a polyacidic region associated with helix alpha 5', the orientation of which is particular to this subgroup, provides a safe haven for the polybasic region when retracted within the interface. Together, these results suggest a mechanism which couples GTP binding and hydrolysis to membrane association and implies a unique role for the SEPT3 subgroup in this process. These observations can be accounted for by constellations of specific amino-acid residues that are found only in this subgroup and by the absence of the C-terminal coiled coil. Such conclusions can only be reached owing to the completeness of the structural studies presented here. (AU)

FAPESP's process: 10/20290-5 - Structural studies of human septins complex
Grantee:Joci Neuby Alves Macedo
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 16/19734-2 - Molecular recognition in septins: the interface studies between SEPT7 and SEPT12
Grantee:Danielle Karoline Silva Do Vale Castro
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 16/04658-9 - Structural determinants for specific interaction of interfaces G and NC of septins: validating the substitution rules in the assembly of the filament
Grantee:Diego Antonio Leonardo Cabrejos
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/00268-0 - Investigation of Aspects Important in the Structural Assembly of Human Septin Filaments
Grantee:Sabrina Matos de Oliveira da Silva
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 14/15546-1 - Septins: comparative studies and the correlation between structure and function
Grantee:Richard Charles Garratt
Support Opportunities: Research Projects - Thematic Grants