De novo design and molecular assembly of a transmembrane diporphyrin-binding protein complex.
By I. Korendovych, Alessandro Senes, Yong Ho Kim, J. D. Lear, H. Fry, M. Therien, J. Blasie, F. Walker, William F. DeGrado. 2010
114 citations recorded by the source corpus.
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.
Subfields: Electrical and Electronic Engineering, Materials Chemistry, Molecular Biology
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Materials Chemistry
- I. Samish
- Xingjie Pan
- Tanja Kortemme
- William F. DeGrado
- I. Korendovych
- David Baker
- Jeffrey J. Gray
- Jens Meiler
In Molecular Biology
- I. Samish
- Xingjie Pan
- Tanja Kortemme
- William F. DeGrado
- I. Korendovych
- David Baker
- Jeffrey J. Gray
- Colin A. Smith
Citations in the corpus
- De novo protein design, a retrospective (2020, background): “10b) (Korendovych et al., 2010).”
- Recent advances in de novo protein design: Principles, methods, and applications (2021, background): “Membrane-spanning peptides that self-assemble into helical bundles were designed to perform functions such as cofactor binding (146) and ion transport (24).”
- Achievements and Challenges in Computational Protein Design. (2017, background): “In 2010 the DeGrado, Therien, Blasie and Walker labs de novo designed a TM diporphyrin-binding protein complex [81].”