The dimerization mechanism of the N-terminal domain of spider silk proteins is conserved despite extensive sequence divergence.


Journal

The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R

Informations de publication

Date de publication:
05 2022
Historique:
received: 15 02 2022
revised: 04 04 2022
accepted: 05 04 2022
pubmed: 11 4 2022
medline: 7 6 2022
entrez: 10 4 2022
Statut: ppublish

Résumé

The N-terminal (NT) domain of spider silk proteins (spidroins) is crucial for their storage at high concentrations and also regulates silk assembly. NTs from the major ampullate spidroin (MaSp) and the minor ampullate spidroin are monomeric at neutral pH and confer solubility to spidroins, whereas at lower pH, they dimerize to interconnect spidroins in a fiber. This dimerization is known to result from modulation of electrostatic interactions by protonation of well-conserved glutamates, although it is undetermined if this mechanism applies to other spidroin types as well. Here, we determine the solution and crystal structures of the flagelliform spidroin NT, which shares only 35% identity with MaSp NT, and investigate the mechanisms of its dimerization. We show that flagelliform spidroin NT is structurally similar to MaSp NT and that the electrostatic intermolecular interaction between Asp 40 and Lys 65 residues is conserved. However, the protonation events involve a different set of residues than in MaSp, indicating that an overall mechanism of pH-dependent dimerization is conserved but can be mediated by different pathways in different silk types.

Identifiants

pubmed: 35398358
pii: S0021-9258(22)00353-2
doi: 10.1016/j.jbc.2022.101913
pmc: PMC9097459
pii:
doi:

Substances chimiques

Silk 0
Fibroins 9007-76-5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101913

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

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Auteurs

Médoune Sarr (M)

Division for Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Kristine Kitoka (K)

Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Riga, Latvia.

Kellie-Ann Walsh-White (KA)

Division for Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.

Margit Kaldmäe (M)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.

Rimants Metlāns (R)

Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Riga, Latvia.

Kaspar Tārs (K)

Latvian Biomedical Research and Study Centre, Riga, Latvia.

Alessandro Mantese (A)

ZoBio BV, Leiden, The Netherlands.

Dipen Shah (D)

ZoBio BV, Leiden, The Netherlands.

Michael Landreh (M)

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, Sweden.

Anna Rising (A)

Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden; Department of Biosciences and Nutrition, Neo, Karolinska Institutet, Huddinge, Sweden.

Jan Johansson (J)

Division for Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Biosciences and Nutrition, Neo, Karolinska Institutet, Huddinge, Sweden.

Kristaps Jaudzems (K)

Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Riga, Latvia. Electronic address: kristaps.jaudzems@osi.lv.

Nina Kronqvist (N)

Division for Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Biosciences and Nutrition, Neo, Karolinska Institutet, Huddinge, Sweden. Electronic address: nina.kronqvist@ki.se.

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Classifications MeSH