Packing of apolar side chains enables accurate design of highly stable membrane proteins.

ABSTRACT: The features that stabilize the structures of membrane proteins remain poorly understood. Polar interactions contribute modestly, and the hydrophobic effect contributes little to the energetics of apolar side-chain packing in membranes. Disruption of steric packing can destabilize the native folds of membrane proteins, but is packing alone sufficient to drive folding in lipids? If so, then membrane proteins stabilized by this feature should be readily designed and structurally characterized-yet this has not been achieved. Through simulation of the natural protein phospholamban and redesign of variants, we define a steric packing code underlying its assembly. Synthetic membrane proteins designed using this code and stabilized entirely by apolar side chains conform to the intended fold. Alth

SUBMITTER: Mravic M 

PROVIDER: S-EPMC7380683 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature