6ZT1

Two states of a de novo hexameric coiled coil assembly CC-Type2-(LaIdGe)4

Summary for 6ZT1

• Entry DOI: 10.2210/pdb6zt1/pdb
• Descriptor: CC-Type2-(LaIdGe)4 (2 entities in total)
• Functional Keywords: coiled coil, de novo peptide, multi-state, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 12
• Total formula weight: 38623.52

Authors

Rhys, G.G.,Brady, R.L.,Woolfson, D.N. (deposition date: 2020-07-17, release date: 2021-02-03, Last modification date: 2021-04-07)

Primary citation

Dawson, W.M.,Lang, E.J.M.,Rhys, G.G.,Shelley, K.L.,Williams, C.,Brady, R.L.,Crump, M.P.,Mulholland, A.J.,Woolfson, D.N.
Structural resolution of switchable states of a de novo peptide assembly.
Nat Commun, 12:1530-1530, 2021

PubMed Abstract: De novo protein design is advancing rapidly. However, most designs are for single states. Here we report a de novo designed peptide that forms multiple α-helical-bundle states that are accessible and interconvertible under the same conditions. Usually in such designs amphipathic α helices associate to form compact structures with consolidated hydrophobic cores. However, recent rational and computational designs have delivered open α-helical barrels with functionalisable cavities. By placing glycine judiciously in the helical interfaces of an α-helical barrel, we obtain both open and compact states in a single protein crystal. Molecular dynamics simulations indicate a free-energy landscape with multiple and interconverting states. Together, these findings suggest a frustrated system in which steric interactions that maintain the open barrel and the hydrophobic effect that drives complete collapse are traded-off. Indeed, addition of a hydrophobic co-solvent that can bind within the barrel affects the switch between the states both in silico and experimentally.

PubMed: 33750792
DOI: 10.1038/s41467-021-21851-8

Experimental method

X-RAY DIFFRACTION (2.01 Å)