Modified integrin polypeptides, modified integrin polypeptide dimers, and uses thereof
<p>The inventors have engineered modified integrin polypeptides by introducing cysteine mutations to enable covalent disulfide bond formation between the α and β subunits. This prevents subunit dissociation and enables formation of stable, crystallizable integrin heterodimers. The cysteine substitutions are designed based on the crystal structure to be distal from the ligand binding site, so they do not impair ligand interactions. The patent provides modified αV and β6 subunit polypeptides as examples. Various cysteine mutation combinations are described that enable heterodimerization of full-length or fragment polypeptides containing key integrin headpiece domains. Importantly, the disulfide-linked heterodimers retain integrin binding capabilities, allowing their use in biochemical and structural studies.</p>
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