Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk

  • Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function.
Metadaten
Author:Julia C. Heiby, Benedikt Goretzki, Christopher M. Johnson, Ute Hellmich, Hannes Neuweiler
URN:urn:nbn:de:hebis:30:3-512788
DOI:https://doi.org/10.1038/s41467-019-12365-5
ISSN:2041-1723
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31558722
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/09/26
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/10/14
Tag:Circular dichroism; Fluorescence spectroscopy; Protein folding; Solution-state NMR
Volume:10
Issue:1, Art. 4378
Page Number:14
First Page:1
Last Page:14
Note:
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/.
HeBIS-PPN:455372284
Institutes:Wissenschaftliche Zentren und koordinierte Programme / Zentrum für Biomolekulare Magnetische Resonanz (BMRZ)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 59 Tiere (Zoologie) / 590 Tiere (Zoologie)
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0