On the emergence of orientational order in folded proteins with implications for allostery

TL;DR

This paper investigates the orientational order in protein structures, revealing that their aperiodic arrangements exhibit nematic properties that are crucial for their mechanical resilience and allosteric functions.

Contribution

It introduces a novel analysis of protein secondary structural elements using nematic order parameters, linking structural order to functional allostery.

Findings

Proteins display nematic droplet behavior with broad $P_{2}$ distribution.

Non-zero $P_{2}$ values correlate with mechanical force resistance.

Structural order supports allosteric signaling mechanisms.

Abstract

The beautiful structures of single and multi-domain proteins are clearly ordered in some fashion but cannot be readily classified using group theory methods that are successfully used to describe periodic crystals. For this reason, protein structures are considered to be aperiodic, and may have evolved this way for functional purposes, especially in instances that require a combination of softness and rigidity within the same molecule. By analyzing the solved protein structures, we show that orientational symmetry is broken in the aperiodic arrangement of the secondary structural elements (SSEs), which we deduce by calculating the nematic order parameter, $P_{2}$. We find that the folded structures are nematic droplets with a broad distribution of $P_{2}$. We argue that non-zero values of $P_{2}$, leads to an arrangement of the SSEs that can resist mechanical forces, which is a requirement for allosteric proteins. Such proteins, which resist mechanical forces in some regions while being flexible in others, transmit signals from one region of the protein to another (action at a distance) in response to binding of ligands (oxygen, ATP or other small molecules).