Common attributes of native-state structures of proteins, disordered proteins, and amyloid.
We show that a framework derived from the common character of globular proteins can be used to understand the design of protein sequences, the behavior of intrinsically unstructured proteins, and the formation of amyloid fibrils in a unified manner. Our studies provide compelling support for the idea that protein native-state structures, the structures adopted by intrinsically unstructured proteins on binding as well as those of amyloid aggregates, all reside in a physical state of matter in which the free energy landscape is sculpted not by the specific sequence of amino acids, but rather by considerations of geometry and symmetry. We elucidate the key role played by sequence design in selecting the structure of choice from the predetermined menu of putative native-state structures.