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Daniel Otzen

Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation

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  • Nina Kronqvist, KI Alzheimer Disease Research Centre, NVS Department, Karolinska Institutet, Novum, 5th floor, SE-141 86 Stockholm, Sweden
  • Martins Otikovs, Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga , Latvia
  • Volodymyr Chmyrov, Experimental Biomolecular Physics, Royal Institute of Technology-KTH, Albanova, SE-106 91 Stockholm, Sweden
  • Gefei Chen, Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai CN-201620, China
  • Marlene Andersson, Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, SE-751 23 Uppsala, Sweden
  • Kerstin Nordling, KI Alzheimer Disease Research Centre, NVS Department, Karolinska Institutet, Novum, 5th floor, SE-141 86 Stockholm, Sweden
  • Michael Landreh, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
  • Médoune Sarr, KI Alzheimer Disease Research Centre, NVS Department, Karolinska Institutet, Novum, 5th floor, SE-141 86 Stockholm, Sweden
  • Hans Jörnvall, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
  • Stefan Wennmalm, 1] Experimental Biomolecular Physics, Royal Institute of Technology-KTH, Albanova, SE-106 91 Stockholm, Sweden [2] Science for Life Laboratory, SE-171 65 Solna, Sweden
  • Jerker Widengren, Experimental Biomolecular Physics, Royal Institute of Technology-KTH, Albanova, SE-106 91 Stockholm, Sweden
  • Qing Meng, Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai CN-201620, China
  • Anna Rising, 1] KI Alzheimer Disease Research Centre, NVS Department, Karolinska Institutet, Novum, 5th floor, SE-141 86 Stockholm, Sweden [2] Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, SE-751 23 Uppsala, Sweden
  • Daniel Otzen
  • Stefan D Knight, Department of Cell and Molecular Biology, Uppsala University, SE-751 24 Uppsala, Sweden
  • Kristaps Jaudzems, Department of Physical Organic Chemistry, Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia
  • Jan Johansson, 1] KI Alzheimer Disease Research Centre, NVS Department, Karolinska Institutet, Novum, 5th floor, SE-141 86 Stockholm, Sweden [2] Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, The Biomedical Centre, SE-751 23 Uppsala, Sweden [3] Institute of Mathematics and Natural Sciences, Tallinn University, Narva mnt 25, EE-101 20 Tallinn, Estonia
The mechanisms controlling the conversion of spider silk proteins into insoluble fibres, which happens in a fraction of a second and in a defined region of the silk glands, are still unresolved. The N-terminal domain changes conformation and forms a homodimer when pH is lowered from 7 to 6; however, the molecular details still remain to be determined. Here we investigate site-directed mutants of the N-terminal domain from Euprosthenops australis major ampullate spidroin 1 and find that the charged residues D40, R60 and K65 mediate intersubunit electrostatic interactions. Protonation of E79 and E119 is required for structural conversions of the subunits into a dimer conformation, and subsequent protonation of E84 around pH 5.7 leads to the formation of a fully stable dimer. These residues are highly conserved, indicating that the now proposed three-step mechanism prevents premature aggregation of spidroins and enables fast formation of spider silk fibres in general.
Original languageEnglish
Article number3254
JournalNature Communications
Volume5
Number of pages11
ISSN2041-1723
DOIs
Publication statusPublished - 10 Feb 2014

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