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Forced Detachment of the CD2-CD58 Complex

The force-induced detachment of the adhesion protein complex CD2-CD58 was studied by steered molecular dynamics simulations. The forced detachment of CD2 and CD58 shows that the system can respond to an external force by two mechanisms, which depend on the loading rate. At the rapid loading rates of...

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Published in:Biophysical journal 2003-04, Vol.84 (4), p.2223-2233
Main Authors: Bayas, M.V., Schulten, K., Leckband, D.
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Leckband, D.
description The force-induced detachment of the adhesion protein complex CD2-CD58 was studied by steered molecular dynamics simulations. The forced detachment of CD2 and CD58 shows that the system can respond to an external force by two mechanisms, which depend on the loading rate. At the rapid loading rates of 70 and 35 pN/ps (pulling speeds of 1 and 0.5 Å/ps) the two proteins unfold before they separate, whereas at slower loading rates of 7 and 3.5 pN/ps (pulling speeds of 0.1 and 0.05 Å/ps), the proteins separate before the domains can unfold. When subjected to a constant force of 400 pN, the two proteins separated without significant structural distortion. These findings suggest that protein unfolding is not coupled to the adhesive function of CD2 and CD58. The simulations further confirm that salt bridges primarily determine the tensile strength of the protein-to-protein bond, and that the order of salt bridge rupture depends mainly on the position of the bond, relative to the line of action of the applied force. Salt bridges close to this line break first. The importance of each of the salt bridges for adhesion, determined from the simulations, correlates closely with their role in cell-to-cell adhesion and equilibrium binding determined by site-directed mutagenesis experiments.
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subjects Binding Sites
Biophysical Theory and Modeling
CD2 Antigens - chemistry
CD58 Antigens - chemistry
Cell Adhesion
Computer Simulation
Crystallography - methods
Macromolecular Substances
Models, Molecular
Molecules
Motion
Protein Binding
Protein Conformation
Protein Denaturation
Protein Folding
Protein Structure, Tertiary
Proteins
Static Electricity
Stress, Mechanical
Structure-Activity Relationship
Tensile Strength
title Forced Detachment of the CD2-CD58 Complex
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