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.
Author:Julia C. Heiby, Benedikt Goretzki, Christopher M. Johnson, Ute Hellmich, Hannes Neuweiler
Pubmed Id:
Parent Title (English):Nature Communications
Publisher:Nature Publishing Group UK
Place of publication:[London]
Document Type:Article
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
Issue:1, Art. 4378
Page Number:14
First Page:1
Last Page:14
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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)
Licence (German):License LogoCreative Commons - Namensnennung 4.0