The Structure of the β-Propeller Domain and C-terminal Region of the Integrin αM Subunit: DEPENDENCE ON β SUBUNIT ASSOCIATION AND PREDICTION OF DOMAINS

Chafen Lu,Claus Oxvig,Timothy A Springer

doi:10.1074/jbc.273.24.15138

Abstract

The Structure of the β-Propeller Domain and C-terminal Region of the Integrin αM Subunit: DEPENDENCE ON β SUBUNIT ASSOCIATION AND PREDICTION OF DOMAINS

Highlights

The integrin family of adhesion molecules participate in important cell-cell and cell-extracellular matrix interactions in a diverse range of biological processes [1]
Electron microscopic images of integrins reveal that the N-terminal portions of the ␣ and ␤ subunits fold into a globular head that is connected to the membrane by two rodlike segments about 16 nm long corresponding to the C-terminal portions of the ␣ and ␤ extracellular domains (20 –22)
MAbs to the ␤-Propeller Domain and a Subset of monoclonal antibodies (mAbs) to the C-terminal Region Do Not React with the Unassociated ␣M Subunit—To study whether folding of the ␣M subunit is dependent on association with the ␤2 subunit, we examined the expression of mAb epitopes on the unassociated ␣M subunit

Summary

Introduction

The integrin family of adhesion molecules participate in important cell-cell and cell-extracellular matrix interactions in a diverse range of biological processes [1]. The integrin ␤ subunits contain a conserved domain of about 250 amino acids in the N-terminal portion This domain has been predicted to have an “I-domainlike” fold [14, 18, 19]. Since mAbs specific for the region of the ␣L subunit C-terminal to the ␤-propeller domain have not been described, it is not known whether folding of this region is dependent on association with the ␤ subunit. Compared with the previous studies on LFA-1, our studies on the ␤-propeller domain are more definitive, since mAb specificity is defined to individual amino acid substitutions between mouse and human, and mAb to epitopes that are widely separated in the predicted ␤-propeller structure all show a dependence on ␤ subunit association for reactivity. Much of the C-terminal region of the ␣M subunit appears to assume a native fold independently of association with the ␤2 subunit

Methods

Results

Conclusion