Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2020
|
Materias: | |
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 |
_version_ | 1783529514812309504 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7201284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT castrodaniellekarolinesilvadovale acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT dasilvasabrinamatosdeoliveira acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT pereirahumbertodmuniz acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT macedojocineubyalves acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT leonardodiegoantonio acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT valadaresnapoleaofonseca acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT kumagaipatriciasuemy acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT brandaonetojose acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT araujoanapaulaulian acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT garrattrichardcharles acompletecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT castrodaniellekarolinesilvadovale completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT dasilvasabrinamatosdeoliveira completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT pereirahumbertodmuniz completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT macedojocineubyalves completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT leonardodiegoantonio completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT valadaresnapoleaofonseca completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT kumagaipatriciasuemy completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT brandaonetojose completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT araujoanapaulaulian completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface AT garrattrichardcharles completecompendiumofcrystalstructuresforthehumansept3subgrouprevealsfunctionalplasticityataspecificseptininterface |