Direction Matters: Monovalent Streptavidin/Biotin Complex under Load

Steffen M. Sedlak, Leonard C. Schendel, Marcelo C.R. Melo, Diana A. Pippig, Zaida Luthey-Schulten, Hermann E. Gaub, Rafael C. Bernardi

Research output: Contribution to journalArticle

Abstract

Novel site-specific attachment strategies combined with improvements of computational resources enable new insights into the mechanics of the monovalent biotin/streptavidin complex under load and forced us to rethink the diversity of rupture forces reported in the literature. We discovered that the mechanical stability of this complex depends strongly on the geometry in which force is applied. By atomic force microscopy-based single molecule force spectroscopy we found unbinding of biotin to occur beyond 400 pN at force loading rates of 10 nN/s when monovalent streptavidin was tethered at its C-terminus. This value is about twice as high than that for N-terminal attachment. Steered molecular dynamics simulations provided a detailed picture of the mechanics of the unbinding process in the corresponding force loading geometries. Using machine learning techniques, we connected findings from hundreds of simulations to the experimental results, identifying different force propagation pathways. Interestingly, we observed that depending on force loading geometry, partial unfolding of N-terminal region of monovalent streptavidin occurs before biotin is released from the binding pocket.

Original languageEnglish (US)
Pages (from-to)3415-3421
Number of pages7
JournalNano letters
Volume19
Issue number6
DOIs
StatePublished - Jun 12 2019

Keywords

  • Streptavidin/biotin
  • atomic force microscopy
  • machine learning
  • molecular dynamics
  • single-molecule force spectroscopy

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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  • Cite this

    Sedlak, S. M., Schendel, L. C., Melo, M. C. R., Pippig, D. A., Luthey-Schulten, Z., Gaub, H. E., & Bernardi, R. C. (2019). Direction Matters: Monovalent Streptavidin/Biotin Complex under Load. Nano letters, 19(6), 3415-3421. https://doi.org/10.1021/acs.nanolett.8b04045