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Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex

Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture...

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Autores principales: Lu, Defen, Shang, Guijun, He, Xiaojing, Bai, Xiao-chen, Zhang, Xuewu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155012/
https://www.ncbi.nlm.nih.gov/pubmed/34039996
http://dx.doi.org/10.1038/s41467-021-23541-x
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author Lu, Defen
Shang, Guijun
He, Xiaojing
Bai, Xiao-chen
Zhang, Xuewu
author_facet Lu, Defen
Shang, Guijun
He, Xiaojing
Bai, Xiao-chen
Zhang, Xuewu
author_sort Lu, Defen
collection PubMed
description Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture of and the molecular interactions in the Sema3/plexin/neuropilin complex are incompletely understood. Here we present the cryo-EM structure of a near intact extracellular region complex of Sema3A, PlexinA4 and Neuropilin 1 (Nrp1) at 3.7 Å resolution. The structure shows a large symmetric 2:2:2 assembly in which each subunit makes multiple interactions with others. The two PlexinA4 molecules in the complex do not interact directly, but their membrane proximal regions are close to each other and poised to promote the formation of the intracellular active dimer for signaling. The structure reveals a previously unknown interface between the a2b1b2 module in Nrp1 and the Sema domain of Sema3A. This interaction places the a2b1b2 module at the top of the complex, far away from the plasma membrane where the transmembrane regions of Nrp1 and PlexinA4 embed. As a result, the region following the a2b1b2 module in Nrp1 must span a large distance to allow the connection to the transmembrane region, suggesting an essential role for the long non-conserved linkers and the MAM domain in neuropilin in the semaphorin/plexin/neuropilin complex.
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spelling pubmed-81550122021-06-11 Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex Lu, Defen Shang, Guijun He, Xiaojing Bai, Xiao-chen Zhang, Xuewu Nat Commun Article Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance and other processes. Despite extensive investigations, the overall architecture of and the molecular interactions in the Sema3/plexin/neuropilin complex are incompletely understood. Here we present the cryo-EM structure of a near intact extracellular region complex of Sema3A, PlexinA4 and Neuropilin 1 (Nrp1) at 3.7 Å resolution. The structure shows a large symmetric 2:2:2 assembly in which each subunit makes multiple interactions with others. The two PlexinA4 molecules in the complex do not interact directly, but their membrane proximal regions are close to each other and poised to promote the formation of the intracellular active dimer for signaling. The structure reveals a previously unknown interface between the a2b1b2 module in Nrp1 and the Sema domain of Sema3A. This interaction places the a2b1b2 module at the top of the complex, far away from the plasma membrane where the transmembrane regions of Nrp1 and PlexinA4 embed. As a result, the region following the a2b1b2 module in Nrp1 must span a large distance to allow the connection to the transmembrane region, suggesting an essential role for the long non-conserved linkers and the MAM domain in neuropilin in the semaphorin/plexin/neuropilin complex. Nature Publishing Group UK 2021-05-26 /pmc/articles/PMC8155012/ /pubmed/34039996 http://dx.doi.org/10.1038/s41467-021-23541-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lu, Defen
Shang, Guijun
He, Xiaojing
Bai, Xiao-chen
Zhang, Xuewu
Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title_full Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title_fullStr Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title_full_unstemmed Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title_short Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex
title_sort architecture of the sema3a/plexina4/neuropilin tripartite complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155012/
https://www.ncbi.nlm.nih.gov/pubmed/34039996
http://dx.doi.org/10.1038/s41467-021-23541-x
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