A structure/function analysis of the integrin beta(1) subunit
The integrins are a family of receptors involved in both cell-matrix and cell-cell interactions. They are heterodimers consisting of an a subunit non-covalently associated with a $\beta$ subunit. Each integrin heterodimer forms a transmembrane complex with the extracellular domain interacting with a ligand and the intracellular domain interacting with cytoskeletal elements. As a way to identify the functional domains on the $\beta\sb1$ subunit, the epitopes for a panel of chicken $\beta\sb1$-specific mAbs that interfere with particular integrin functions were determined. The epitopes for one set of mAbs that block ligand binding were mapped toward the N-terminal 200 residues. Residues 141 to 160 may fit into an $\alpha$-helix and a peptide of this sequence perturbed the binding between the $\beta\sb1$ integrin and fibronectin. A second set of mAbs that either block ligand binding, alter ligand specificity or induce $\alpha/\beta$ subunit dissociation were mapped to a region near the transmembrane segment. These data suggest a portion of $\beta\sb1$ ligand binding domain rests within the first 200 residues and a regulatory domain, that affects ligand binding through secondary conformational changes, resides in a region close to the transmembrane domain. To investigate the structural basis of the functional linkage between these two domains, cysteine residues implicated in long-range disulfide bond formation were mutated and the functional effects examined. The results showed that subtle structural changes of the $\beta\sb1$ subunit affect events subsequent to ligand binding, including sub-cellular localization, matrix assembly, cell migration and signal transduction.
Shih, Daw-Tsun, "A structure/function analysis of the integrin beta(1) subunit" (1994). Dissertations available from ProQuest. AAI9427614.