Impact of Salt Bridges on the Equilibrium Binding and Adhesion of Human CD2 and CD58

This study describes quantitative investigations of the impact of single charge mutations on equilibrium binding, kinetics, and the adhesion strength of the CD2-CD58 interaction. Previously steered molecular dynamics simulations guided the selection of the charge mutants investigated, which include...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2007-02, Vol.282 (8), p.5589-5596
Main Authors: Bayas, Marco V., Kearney, Alice, Avramovic, Adam, van der Merwe, P. Anton, Leckband, Deborah E.
Format: Article
Language:English
Subjects:
Amino Acid Substitution
CD2 Antigens - chemistry
CD2 Antigens - genetics
CD2 Antigens - metabolism
CD58 Antigens - chemistry
CD58 Antigens - genetics
CD58 Antigens - metabolism
Cell Adhesion - physiology
Humans
Models, Molecular
Protein Binding - genetics
Protein Structure, Quaternary
Protein Structure, Tertiary
Salts - chemistry
Salts - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study describes quantitative investigations of the impact of single charge mutations on equilibrium binding, kinetics, and the adhesion strength of the CD2-CD58 interaction. Previously steered molecular dynamics simulations guided the selection of the charge mutants investigated, which include the CD2 mutants D31A, K41A, K51A, and K91A. This set includes mutations in which the previous cell aggregation and binding data either agreed or disagreed with the steered molecular dynamics predictions. Surface plasmon resonance measurements quantified the solution binding properties. Adhesion was quantified with the surface force apparatus, which was used previously to study the closely related CD2-CD48 interaction. The results reveal roles that these salt bridges play in equilibrium binding and adhesion. We discuss both the molecular basis of this behavior and its implications for cell adhesion.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M607968200