8EK4

De novo designed ice-binding proteins from twist-constrained helices

Summary for 8EK4

• Entry DOI: 10.2210/pdb8ek4/pdb
• Descriptor: Ice-binding protein TIP-99a (1 entity in total)
• Functional Keywords: de novo designed, ice-binding proteins, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 33191.75

Authors

Bera, A.K.,De Haas, R.J. (deposition date: 2022-09-19, release date: 2023-07-12, Last modification date: 2024-04-03)

Primary citation

de Haas, R.J.,Tas, R.P.,van den Broek, D.,Zheng, C.,Nguyen, H.,Kang, A.,Bera, A.K.,King, N.P.,Voets, I.K.,de Vries, R.
De novo designed ice-binding proteins from twist-constrained helices.
Proc.Natl.Acad.Sci.USA, 120:e2220380120-e2220380120, 2023

PubMed Abstract: Attaining molecular-level control over solidification processes is a crucial aspect of materials science. To control ice formation, organisms have evolved bewildering arrays of ice-binding proteins (IBPs), but these have poorly understood structure-activity relationships. We propose that reverse engineering using de novo computational protein design can shed light on structure-activity relationships of IBPs. We hypothesized that the model alpha-helical winter flounder antifreeze protein uses an unusual undertwisting of its alpha-helix to align its putative ice-binding threonine residues in exactly the same direction. We test this hypothesis by designing a series of straight three-helix bundles with an ice-binding helix projecting threonines and two supporting helices constraining the twist of the ice-binding helix. Our findings show that ice-recrystallization inhibition by the designed proteins increases with the degree of designed undertwisting, thus validating our hypothesis, and opening up avenues for the computational design of IBPs.

PubMed: 37364125
DOI: 10.1073/pnas.2220380120

Experimental method

X-RAY DIFFRACTION (2.35 Å)