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

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 hexameri...

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Autores principales: Castro, Danielle Karoline Silva do Vale, da Silva, Sabrina Matos de Oliveira, Pereira, Humberto D’Muniz, Macedo, Joci Neuby Alves, Leonardo, Diego Antonio, Valadares, Napoleão Fonseca, Kumagai, Patricia Suemy, Brandão-Neto, José, Araújo, Ana Paula Ulian, Garratt, Richard Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201284/
https://www.ncbi.nlm.nih.gov/pubmed/32431830
http://dx.doi.org/10.1107/S2052252520002973
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author Castro, Danielle Karoline Silva do Vale
da Silva, Sabrina Matos de Oliveira
Pereira, Humberto D’Muniz
Macedo, Joci Neuby Alves
Leonardo, Diego Antonio
Valadares, Napoleão Fonseca
Kumagai, Patricia Suemy
Brandão-Neto, José
Araújo, Ana Paula Ulian
Garratt, Richard Charles
author_facet Castro, Danielle Karoline Silva do Vale
da Silva, Sabrina Matos de Oliveira
Pereira, Humberto D’Muniz
Macedo, Joci Neuby Alves
Leonardo, Diego Antonio
Valadares, Napoleão Fonseca
Kumagai, Patricia Suemy
Brandão-Neto, José
Araújo, Ana Paula Ulian
Garratt, Richard Charles
author_sort Castro, Danielle Karoline Silva do Vale
collection PubMed
description 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.
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spelling pubmed-72012842020-05-19 A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface Castro, Danielle Karoline Silva do Vale da Silva, Sabrina Matos de Oliveira Pereira, Humberto D’Muniz Macedo, Joci Neuby Alves Leonardo, Diego Antonio Valadares, Napoleão Fonseca Kumagai, Patricia Suemy Brandão-Neto, José Araújo, Ana Paula Ulian Garratt, Richard Charles IUCrJ Research Papers 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. International Union of Crystallography 2020-03-28 /pmc/articles/PMC7201284/ /pubmed/32431830 http://dx.doi.org/10.1107/S2052252520002973 Text en © Danielle Karoline Silva do Vale Castro et al. 2020 http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/4.0/
spellingShingle Research Papers
Castro, Danielle Karoline Silva do Vale
da Silva, Sabrina Matos de Oliveira
Pereira, Humberto D’Muniz
Macedo, Joci Neuby Alves
Leonardo, Diego Antonio
Valadares, Napoleão Fonseca
Kumagai, Patricia Suemy
Brandão-Neto, José
Araújo, Ana Paula Ulian
Garratt, Richard Charles
A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title_full A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title_fullStr A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title_full_unstemmed A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title_short A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface
title_sort complete compendium of crystal structures for the human sept3 subgroup reveals functional plasticity at a specific septin interface
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201284/
https://www.ncbi.nlm.nih.gov/pubmed/32431830
http://dx.doi.org/10.1107/S2052252520002973
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