Resolving Speed and Encoding Bottlenecks in Fast Heteromeric Self-Assembly

TL;DR

This paper investigates the kinetic and encoding bottlenecks in heteromeric self-assembly of proteins, proposing that increasing connectivity of key components can enhance assembly speed and accuracy, with implications for biological processes.

Contribution

It extends a heteropolymer growth model to include structure retrieval, revealing how boosting connectivity of select components can overcome assembly bottlenecks.

Findings

Bottlenecks significantly slow down self-assembly.

Increasing connectivity of a few components suppresses bottlenecks.

Kinetic control of critical binding events explains efficient assembly.

Abstract

The cytoplasm is a heterogeneous mixture containing many types of proteins that self-assemble into a wide variety of complexes. The accuracy and speed of cytoplasmic self-assembly is astonishing because it involves the correct identification of components shared among different structures, despite pervasive thermal fluctuations. Typical toy models of self-assembly are based on the specificity of binding energies among components and neglect kinetic effects. However, kinetics plays a key role in biological self-assembly, often catalyzed by a plethora of assembly factors. Building on this observation, we extend a previous heteropolymer growth model to describe the retrieval of two-dimensional structures. We find that the self-assembly of structures in this model is subject to strong speed and encoding bottlenecks. Moreover, we show that these bottlenecks can be suppressed by increasing the connectivity of a small fraction of components. This mechanism of kinetically controlling a small number of critical binding events provides a simple explanation for the timely assembly of large protein, and suggests a unifying principle for the role of assembly factors.