De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex

Ivan V. Korendovych, Alessandro Senes, Yong Ho Kim, James D. Lear, H. Christopher Fry, Michael J. Therien, J. Kent Blasie, F. Ann Walker, William F. Degrado

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

The de novo design of membrane proteins remains difficult despite recent advances in understanding the factors that drive membrane protein folding and association. We have designed a membrane protein PRIME (PoRphyrins In MEmbrane) that positions two non-natural iron diphenylporphyrins (FeIIIDPP's) sufficiently close to provide a multicentered pathway for transmembrane electron transfer. Computational methods previously used for the design of multiporphyrin water-soluble helical proteins were extended to this membrane target. Four helices were arranged in a D2-symmetrical bundle to bind two Fe(II/III) diphenylporphyrins in a bis-His geometry further stabilized by second-shell hydrogen bonds. UV-vis absorbance, CD spectroscopy, analytical ultracentrifugation, redox potentiometry, and EPR demonstrate that PRIME binds the cofactor with high affinity and specificity in the expected geometry.

Original languageEnglish (US)
Pages (from-to)15516-15518
Number of pages3
JournalJournal of the American Chemical Society
Volume132
Issue number44
DOIs
StatePublished - Nov 10 2010

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Korendovych, I. V., Senes, A., Kim, Y. H., Lear, J. D., Fry, H. C., Therien, M. J., Blasie, J. K., Walker, F. A., & Degrado, W. F. (2010). De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex. Journal of the American Chemical Society, 132(44), 15516-15518. https://doi.org/10.1021/ja107487b