{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mravic M"],"funding":["Howard Hughes Medical Institute","National Institute of General Medical Sciences","NIGMS NIH HHS","National Science Foundation"],"pagination":["1418-1423"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7380683"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["363(6434)"],"pubmed_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. Although highly stable, the steric complementarity required for their folding is surprisingly stringent. Structural informatics shows that the designed packing motif recurs across the proteome, emphasizing a prominent role for precise apolar packing in membrane protein folding, stabilization, and evolution."],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Packing of apolar side chains enables accurate design of highly stable membrane proteins."],"pmcid":["PMC7380683"],"funding_grant_id":["T32 GM008284","R01 GM124149","R01 GM117593","P30 GM124169","R35 GM122603","CHE-1413295","R01GM117593","NIGMS R35-122603"],"pubmed_authors":["Liu L","Solomon PE","Mravic M","DeGrado WF","Tucker M","Thomaston JL"],"additional_accession":[]},"is_claimable":false,"name":"Packing of apolar side chains enables accurate design of highly stable membrane proteins.","description":"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. Although highly stable, the steric complementarity required for their folding is surprisingly stringent. Structural informatics shows that the designed packing motif recurs across the proteome, emphasizing a prominent role for precise apolar packing in membrane protein folding, stabilization, and evolution.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Mar","modification":"2026-05-03T00:05:13.885Z","creation":"2020-09-11T07:09:59Z"},"accession":"S-EPMC7380683","cross_references":{"pubmed":["30923216"],"doi":["10.1126/science.aav7541"]}}