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A conserved spider silk domain acts as a molecular switch that controls fibre assembly


A huge variety of proteins are able to form fibrillar structures1, especially at high protein concentrations. Hence, it is surprising that spider silk proteins can be stored in a soluble form at high concentrations and transformed into extremely stable fibres on demand2,3. Silk proteins are reminiscent of amphiphilic block copolymers containing stretches of polyalanine and glycine-rich polar elements forming a repetitive core flanked by highly conserved non-repetitive amino-terminal4,5 and carboxy-terminal6 domains. The N-terminal domain comprises a secretion signal, but further functions remain unassigned. The C-terminal domain was implicated in the control of solubility and fibre formation7 initiated by changes in ionic composition8,9 and mechanical stimuli known to align the repetitive sequence elements and promote β-sheet formation10,11,12,13,14. However, despite recent structural data15, little is known about this remarkable behaviour in molecular detail. Here we present the solution structure of the C-terminal domain of a spider dragline silk protein and provide evidence that the structural state of this domain is essential for controlled switching between the storage and assembly forms of silk proteins. In addition, the C-terminal domain also has a role in the alignment of secondary structural features formed by the repetitive elements in the backbone of spider silk proteins, which is known to be important for the mechanical properties of the fibre.

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Figure 1: Sequence analysis and structure of the non-repetitive (NR) domain of ADF-3.
Figure 2: Assembly and aggregation properties of our spider silk-like proteins.
Figure 3: Stability and folding of spider dragline silk constructs.
Figure 4: Fibre assembly mechanism of dragline silk proteins.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

The resonance assignment obtained was deposited at the BMRB data bank under accession code 16249 and the atomic coordinates of the best 20 structures plus a regularized average structure have been deposited at the Protein Data Bank under accession code 2khm.


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This paper is in memoriam of R. Rudolph who triggered spider silk research in the lab of T.S. We want to thank D. Hümmerich and J. Exler for initial work on the project, S. Quedzuweit for sample preparation in early stages of the project, M. Heim and M. Suhre for cloning work, and H. Krause for mass spectrometry. This work was supported by the Center for Integrated Protein Science Munich (CIPSM) (to H.K. and T.S.) and the Deutsche Forschungsgemeinschaft SCHE 603/4-3 (to T.S.). F.H. was supported by the Elitenetzwerk Bayern, CompInt. J.G.H. was supported by the Alexander von Humboldt Foundation.

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Authors and Affiliations



F.H. designed research, performed cloning work, purified proteins, performed protein folding studies, recorded NMR experiments, performed structure calculations and wrote the manuscript; L.E. performed cloning work, purified proteins and performed aggregation assays. J.G.H. performed aggregation assays, characterized the fibres and wrote the manuscript; C.V. performed cloning work and purified proteins; M.C. was involved in structure calculation and provided software tools for structure calculation and analysis; T.S. designed research and wrote the manuscript; H.K. designed research and wrote the manuscript. All authors discussed the results and commented on the manuscript.

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Correspondence to Thomas Scheibel or Horst Kessler.

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The authors declare no competing financial interests.

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Hagn, F., Eisoldt, L., Hardy, J. et al. A conserved spider silk domain acts as a molecular switch that controls fibre assembly. Nature 465, 239–242 (2010).

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