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

J Am Chem Soc. 2010 Nov 10;132(44):15516-8. doi: 10.1021/ja107487b.


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 (Fe(III)DPP'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 D(2)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Circular Dichroism
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Porphyrins / chemistry*
  • Protein Binding
  • Protein Folding


  • Membrane Proteins
  • Multiprotein Complexes
  • Porphyrins