Orientational Ambiguity in Septin Coiled Coils and its Structural Basis
(2021) In Journal of Molecular Biology 433(9).- Abstract
Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These... (More)
Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.
(Less)
- author
- Leonardo, Diego A.
; Cavini, Italo A.
; Sala, Fernanda A.
; Mendonça, Deborah C.
; Rosa, Higor V.D.
; Kumagai, Patricia S.
; Crusca, Edson
; Valadares, Napoleão F.
; Marques, Ivo A.
; Brandão-Neto, José
; Munte, Claudia E.
; Kalbitzer, Hans R.
; Soler, Nicolas
; Usón, Isabel
; André, Ingemar
LU
; Araujo, Ana P.U.
; D'Muniz Pereira, Humberto
and Garratt, Richard C.
(Less) - organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- coiled coil, crystal structures, mixed hydrophobic/hydrophilic interface, protein filament, septins
- in
- Journal of Molecular Biology
- volume
- 433
- issue
- 9
- article number
- 166889
- publisher
- Elsevier
- external identifiers
-
- pmid:33639214
- scopus:85102046058
- ISSN
- 0022-2836
- DOI
- 10.1016/j.jmb.2021.166889
- language
- English
- LU publication?
- yes
- id
- 8f24d864-3b63-406c-86ff-1fb9642d8f82
- date added to LUP
- 2021-03-16 14:41:07
- date last changed
- 2024-06-13 08:36:01
@article{8f24d864-3b63-406c-86ff-1fb9642d8f82,
abstract = {{<p>Septins are an example of subtle molecular recognition whereby different paralogues must correctly assemble into functional filaments important for essential cellular events such as cytokinesis. Most possess C-terminal domains capable of forming coiled coils which are believed to be involved in filament formation and bundling. Here, we report an integrated structural approach which aims to unravel their architectural diversity and in so doing provide direct structural information for the coiled-coil regions of five human septins. Unexpectedly, we encounter dimeric structures presenting both parallel and antiparallel arrangements which are in consonance with molecular modelling suggesting that both are energetically accessible. These sequences therefore code for two metastable states of different orientations which employ different but overlapping interfaces. The antiparallel structures present a mixed coiled-coil interface, one side of which is dominated by a continuous chain of core hydrophilic residues. This unusual type of coiled coil could be used to expand the toolkit currently available to the protein engineer for the design of previously unforeseen coiled-coil based assemblies. Within a physiological context, our data provide the first atomic details related to the assumption that the parallel orientation is likely formed between septin monomers from the same filament whilst antiparallelism may participate in the widely described interfilament cross bridges necessary for higher order structures and thereby septin function.</p>}},
author = {{Leonardo, Diego A. and Cavini, Italo A. and Sala, Fernanda A. and Mendonça, Deborah C. and Rosa, Higor V.D. and Kumagai, Patricia S. and Crusca, Edson and Valadares, Napoleão F. and Marques, Ivo A. and Brandão-Neto, José and Munte, Claudia E. and Kalbitzer, Hans R. and Soler, Nicolas and Usón, Isabel and André, Ingemar and Araujo, Ana P.U. and D'Muniz Pereira, Humberto and Garratt, Richard C.}},
issn = {{0022-2836}},
keywords = {{coiled coil; crystal structures; mixed hydrophobic/hydrophilic interface; protein filament; septins}},
language = {{eng}},
number = {{9}},
publisher = {{Elsevier}},
series = {{Journal of Molecular Biology}},
title = {{Orientational Ambiguity in Septin Coiled Coils and its Structural Basis}},
url = {{http://dx.doi.org/10.1016/j.jmb.2021.166889}},
doi = {{10.1016/j.jmb.2021.166889}},
volume = {{433}},
year = {{2021}},
}