Polymorphic Self‐Assembly with Procedural Flexibility for Monodisperse Quaternary Protein Structures of DegQ Enzymes

Abstract

As large molecular tertiary structures, some proteins can act as small robots that find, bind, and chaperone target protein clients, showing the potential to serve as smart building blocks in self‐assembly fields. Instead of using such intrinsic functions, most self‐assembly methodologies for proteins aim for de novo‐designed structures with accurate geometric assemblies, which could limit procedural flexibility. Here, we present a strategy enabling polymorphic clustering of quaternary proteins, exhibiting simplicity and flexibility of self‐assembling paths for proteins in forming monodisperse quaternary cage particles. We propose that the enzyme protomer DegQ, previously solved at low resolution, may potentially be usable as a threefold symmetric building block, which can form polyhedral cages incorporated by the chaperone action of DegQ in the presence of protein clients. To obtain highly monodisperse cage particles, we utilize soft, and hence, less resistive client proteins, which can program the inherent chaperone activity of DegQ to efficient formations of polymorphic cages, depending on the size of clients. By reconstructing the atomic resolution cryo‐EM DegQ structures using obtained 12‐ and 24‐meric clusters, we validate the polymorphic clustering of DegQ enzymes in terms of soft and rigid domains, which would provide effective routes for protein self‐assemblies with procedural flexibility.This article is protected by copyright. All rights reserved