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Properties of protein unfolded states suggest broad selection for expanded conformational ensembles

2020; National Academy of Sciences; Volume: 117; Issue: 38 Linguagem: Inglês

10.1073/pnas.2003773117

1091-6490

Micayla A. Bowman, Joshua A. Riback, Anabel Rodríguez, Hongyu Guo, Jun Li, Tobin R. Sosnick, Patricia L. Clark,

Enzyme Structure and Function

Significance Amino acid sequences are known to be crucial for specifying the folded structure of a protein. Here we show that sequences also play an important role in specifying the properties of a protein’s unfolded ensemble. For an autotransporter protein, rearranging the order of only a few percent of amino acid residues can lead to more collapsed unfolded ensembles which have enhanced aggregation in vitro and degradation in vivo. Sequences that remain expanded, however, are more compatible with proper function. Most significantly, we show that the well-mixed sequence patterns that lead to expanded ensembles are broadly conserved amongst foldable, water-soluble proteins, suggesting expanded disordered states are under selection.