Cargando…
Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1)
Actinoporins are a family of α-pore-forming toxins (α-PFTs) that have been identified in sea anemones. Recently, a freshwater Hydra Actinoporin-Like Toxin (HALT) gene family was found in Hydra magnipapillata. Unlike sea anemone actinoporins that use sphingomyelin as their main recognition target, th...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526580/ https://www.ncbi.nlm.nih.gov/pubmed/34667248 http://dx.doi.org/10.1038/s41598-021-99879-5 |
_version_ | 1784585899098505216 |
---|---|
author | Ker, De-Sheng Sha, Hong Xi Jonet, Mohd Anuar Hwang, Jung Shan Ng, Chyan Leong |
author_facet | Ker, De-Sheng Sha, Hong Xi Jonet, Mohd Anuar Hwang, Jung Shan Ng, Chyan Leong |
author_sort | Ker, De-Sheng |
collection | PubMed |
description | Actinoporins are a family of α-pore-forming toxins (α-PFTs) that have been identified in sea anemones. Recently, a freshwater Hydra Actinoporin-Like Toxin (HALT) gene family was found in Hydra magnipapillata. Unlike sea anemone actinoporins that use sphingomyelin as their main recognition target, the HALTs proteins may recognise alternative lipid molecules as their target. To unveil the structural insights into lipid preference of HALTs protein as compared to sea anemone actinoporins, we have determined the first crystal structure of actinoporin-like toxin, HALT-1 at 1.43 Å resolution with an acetylated lysine residue K76. Despite the overall structure of HALT-1 sharing a high structural similarity to sea anemone actinoporins, the atomic resolution structure revealed several unique structural features of HALT-1 that may influence the lipid preference and oligomerisation interface. The HALT-1 contains a RAG motif in place of the highly conserved RGD motif found in sea anemone actinoporins. The RAG motif contributed to a sharper β9-β10 turn, which may sway its oligomerisation interface in comparison to sea anemone actinoporins. In the lipid-binding region, the HALT-1 contains a shorter α2 helix and a longer α2-β9 loop due to deletion and subsequently an insertion of five amino acid residues in comparison to the sea anemone actinoporins. Structure comparison and molecular docking analysis further revealed that the HALT-1 lipid-binding site may favour sphingolipids with sulfate or phosphate head group more than the sphingomyelin. The structure of HALT-1 reported here provides a new insight for a better understanding of the evolution and lipid recognition mechanism of actinoporin. |
format | Online Article Text |
id | pubmed-8526580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85265802021-10-20 Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) Ker, De-Sheng Sha, Hong Xi Jonet, Mohd Anuar Hwang, Jung Shan Ng, Chyan Leong Sci Rep Article Actinoporins are a family of α-pore-forming toxins (α-PFTs) that have been identified in sea anemones. Recently, a freshwater Hydra Actinoporin-Like Toxin (HALT) gene family was found in Hydra magnipapillata. Unlike sea anemone actinoporins that use sphingomyelin as their main recognition target, the HALTs proteins may recognise alternative lipid molecules as their target. To unveil the structural insights into lipid preference of HALTs protein as compared to sea anemone actinoporins, we have determined the first crystal structure of actinoporin-like toxin, HALT-1 at 1.43 Å resolution with an acetylated lysine residue K76. Despite the overall structure of HALT-1 sharing a high structural similarity to sea anemone actinoporins, the atomic resolution structure revealed several unique structural features of HALT-1 that may influence the lipid preference and oligomerisation interface. The HALT-1 contains a RAG motif in place of the highly conserved RGD motif found in sea anemone actinoporins. The RAG motif contributed to a sharper β9-β10 turn, which may sway its oligomerisation interface in comparison to sea anemone actinoporins. In the lipid-binding region, the HALT-1 contains a shorter α2 helix and a longer α2-β9 loop due to deletion and subsequently an insertion of five amino acid residues in comparison to the sea anemone actinoporins. Structure comparison and molecular docking analysis further revealed that the HALT-1 lipid-binding site may favour sphingolipids with sulfate or phosphate head group more than the sphingomyelin. The structure of HALT-1 reported here provides a new insight for a better understanding of the evolution and lipid recognition mechanism of actinoporin. Nature Publishing Group UK 2021-10-19 /pmc/articles/PMC8526580/ /pubmed/34667248 http://dx.doi.org/10.1038/s41598-021-99879-5 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ker, De-Sheng Sha, Hong Xi Jonet, Mohd Anuar Hwang, Jung Shan Ng, Chyan Leong Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title | Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title_full | Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title_fullStr | Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title_full_unstemmed | Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title_short | Structural and functional analysis of Hydra Actinoporin-Like Toxin 1 (HALT-1) |
title_sort | structural and functional analysis of hydra actinoporin-like toxin 1 (halt-1) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526580/ https://www.ncbi.nlm.nih.gov/pubmed/34667248 http://dx.doi.org/10.1038/s41598-021-99879-5 |
work_keys_str_mv | AT kerdesheng structuralandfunctionalanalysisofhydraactinoporinliketoxin1halt1 AT shahongxi structuralandfunctionalanalysisofhydraactinoporinliketoxin1halt1 AT jonetmohdanuar structuralandfunctionalanalysisofhydraactinoporinliketoxin1halt1 AT hwangjungshan structuralandfunctionalanalysisofhydraactinoporinliketoxin1halt1 AT ngchyanleong structuralandfunctionalanalysisofhydraactinoporinliketoxin1halt1 |