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

DOI: 10.1107/S2052252520002973 DOI Help

Authors: Danielle Karoline Silva Do Vale Castro (Universidade de São Paulo) , Sabrina Matos De Oliveira Da Silva (Universidade de São Paulo) , Humberto D'muniz Pereira (Universidade de São Paulo) , Joci Neuby Alves Macedo (Universidade de São Paulo; Federal Institute of Education, Science and Technology of Rondonia) , Diego Antonio Leonardo (Universidade de São Paulo) , Napoleao Fonseca Valadares (Universidade de Brasília) , Patricia Suemy Kumagai (Universidade de São Paulo) , Jose Brandao-neto (Diamond Light Source) , Ana Paula Ulian Araújo (Universidade de São Paulo) , Richard Charles Garratt (São Carlos Institute of Physics, University of São Paulo)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Iucrj , VOL 7

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 14493 , 5810

Open Access Open Access

Abstract: 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 GTPγS 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 α5′, 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.

Journal Keywords: septins; GTP binding/hydrolysis; filaments; protein structure; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: ASTRID2; SOLEIL