Integrins are heterodimers consisting of the non-covalently associated α- and β-subunits. Each contain a large N-terminal ectodomain, a transmembrane helix and a C-terminal cytoplasmic region. The vertebrate-specific αI integrins bind ligands through an αI domain within the α-subunit. αMβ2 and αXβ2 are αI integrins and adopts three major conformational states.

In the bent-closed conformation with low ligand affinity, the αI domain is close to the plasma membrane. In the high affinity extended-open conformation, their ectodomains are fully extended and the ”legs” of the two subunits separated. In this conformation, an αI integrin is subject to a tensile force created by two opposing forces arising from:

1. 1. binding of the extracellular ligand to the αI domain;
   2. interaction with the actin cytoskeleton through the β-subunit.

In the extended-closed (EC) conformation with low/intermediate ligand affinity, the two subunits of the integrins are close together and the β-subunit is not linked to actin.

This project focuses on structural studies of the ectodomains and their complexes with modulatory antibodies with potential for treating inflammatory and neurodegenerative disease.