Insight into the Structure of the “Unstructured” Tau Protein

Konstantin I. Popov, Karl A.T. Makepeace, Evgeniy V. Petrotchenko, Nikolay V. Dokholyan, Christoph H. Borchers

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Combining structural proteomics experimental data with computational methods is a powerful tool for protein structure prediction. Here, we apply a recently developed approach for de novo protein structure determination based on the incorporation of short-distance crosslinking data as constraints in discrete molecular dynamics simulations (CL-DMD), for the determination of the conformational ensemble of tau protein in solution. The predicted structures were in agreement with surface modification and long-distance crosslinking data. Tau in solution was found as an ensemble of rather compact globular conformations with distinct topology, inter-residue contacts, and a number of transient secondary-structure elements. Regions important for pathological aggregation consistently were found to contain β strands. The determined structures are compatible with the tau protein in solution being a molten globule at near-ground state with persistent residual structural features which we were able to capture by CL-DMD. The predicted structure may facilitate an understanding of the misfolding and oligomerization pathways of the tau protein.

Original languageEnglish (US)
Pages (from-to)1710-1715.e4
Issue number11
StatePublished - Nov 5 2019

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology


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