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Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS
Non‐ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N‐ and C‐terminal docking domains ((N/C)DDs). Typically, docking domains function independent...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251938/ https://www.ncbi.nlm.nih.gov/pubmed/33876501 http://dx.doi.org/10.1002/anie.202103498 |
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author | Watzel, Jonas Duchardt‐Ferner, Elke Sarawi, Sepas Bode, Helge B. Wöhnert, Jens |
author_facet | Watzel, Jonas Duchardt‐Ferner, Elke Sarawi, Sepas Bode, Helge B. Wöhnert, Jens |
author_sort | Watzel, Jonas |
collection | PubMed |
description | Non‐ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N‐ and C‐terminal docking domains ((N/C)DDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of “designer” NRPS from proteins that normally do not interact. The multiprotein “peptide‐antimicrobial‐Xenorhabdus” (PAX) peptide‐producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small (C)DD of PaxA cooperates with its preceding thiolation (T(1)) domain to bind the (N)DD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems. |
format | Online Article Text |
id | pubmed-8251938 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82519382021-07-07 Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS Watzel, Jonas Duchardt‐Ferner, Elke Sarawi, Sepas Bode, Helge B. Wöhnert, Jens Angew Chem Int Ed Engl Research Articles Non‐ribosomal peptide synthetases (NRPS) produce natural products from amino acid building blocks. They often consist of multiple polypeptide chains which assemble in a specific linear order via specialized N‐ and C‐terminal docking domains ((N/C)DDs). Typically, docking domains function independently from other domains in NRPS assembly. Thus, docking domain replacements enable the assembly of “designer” NRPS from proteins that normally do not interact. The multiprotein “peptide‐antimicrobial‐Xenorhabdus” (PAX) peptide‐producing PaxS NRPS is assembled from the three proteins PaxA, PaxB and PaxC. Herein, we show that the small (C)DD of PaxA cooperates with its preceding thiolation (T(1)) domain to bind the (N)DD of PaxB with very high affinity, establishing a structural and thermodynamical basis for this unprecedented docking interaction, and we test its functional importance in vivo in a truncated PaxS assembly line. Similar docking interactions are apparently present in other NRPS systems. John Wiley and Sons Inc. 2021-05-14 2021-06-14 /pmc/articles/PMC8251938/ /pubmed/33876501 http://dx.doi.org/10.1002/anie.202103498 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Watzel, Jonas Duchardt‐Ferner, Elke Sarawi, Sepas Bode, Helge B. Wöhnert, Jens Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title | Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title_full | Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title_fullStr | Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title_full_unstemmed | Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title_short | Cooperation between a T Domain and a Minimal C‐Terminal Docking Domain to Enable Specific Assembly in a Multiprotein NRPS |
title_sort | cooperation between a t domain and a minimal c‐terminal docking domain to enable specific assembly in a multiprotein nrps |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251938/ https://www.ncbi.nlm.nih.gov/pubmed/33876501 http://dx.doi.org/10.1002/anie.202103498 |
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