Natural β-sheet proteins use negative design to avoid edge-to-edge aggregation

摘要

The fact that natural β-sheet proteins are usually soluble but that fragments or designs of β structure usually aggregate suggests that natural β proteins must somehow be designed to avoid this problem. Regular β-sheet edges are dangerous, because they are already in the right conformation to interact with any other β strand they encounter. We surveyed edge strands in a large sample of all-β proteins to tabulate features that could protect against further β-sheet interactions. β-barrels, of course, avoid edges altogether by continuous H-bonding around the barrel cylinder. Parallel β-helix proteins protect their β-sheet ends by covering them with loops of other structure.