Unbinding and unfolding of adhesion protein complexes through stretching: Interplay between shear and tensile mechanical clamps

TL;DR

This study uses molecular dynamics simulations to investigate how mechanical forces cause dissociation and unfolding of the CD48-2B4 immune protein complex, revealing direction-dependent pathways and force thresholds.

Contribution

It provides the first theoretical analysis of the mechanostability and dissociation pathways of the CD48-2B4 complex under mechanical stress.

Findings

Dissociation pathways depend on pulling direction.

Three interface patches act as units resisting force.

Forces between 100 and 200 pN are needed for dissociation.

Abstract

Using coarse-grained molecular dynamics simulations, we analyze mechanically induced dissociation and unfolding of the protein complex CD48-2B4. This heterodimer is an indispensable component of the immunological system: 2B4 is a receptor on natural killer cells whereas CD48 is expressed on surfaces of various immune cells. So far, its mechanostability has not been assessed either experimentally or theoretically. We find that the dissociation processes strongly depend on the direction of pulling and may take place in several pathways. Interestingly, the CD48-2B4 interface can be divided into three distinct patches that act as units when resisting the pulling forces. At experimentally accessible pulling speeds, the characteristic mechanostability forces are in the range between 100 and 200 pN, depending on the pulling direction. These characteristic forces need not be associated with tensile forces involved in the act of separation of the complex because prior shear-involving unraveling within individual proteins may give rise to a higher force peak.