Nucleation of glucose isomerase protein crystals in a nonclassical disguise: The role of crystalline precursors

Abstract

Significance The ability of proteins to self-assemble into complex, hierarchical structures has been the inspiration for the bottom-up design of a class of biomaterials with proteins as their building blocks. The earliest stages of formation often involve the passing of an activation barrier under the form of nucleus formation, a quaternary protein complex that templates incoming molecules to proper registry. For protein crystallization, the consensus has emerged that the fastest route toward a nucleus follows a winding path: first, densification, followed by symmetry formation. In this contribution, we show that this need not be the case for the protein glucose isomerase, which seems to follow the simplest path to a nucleus, making crystalline clusters from the earliest detectable beginnings.