Fig. 3

Structural components to stabilize inactive integrin conformation. a The cytoplasmic salt bridge is formed between the arginine residue in the α subunit and the glutamate residue in the β subunit, thereby clasping the α/β integrin cytoplasmic tails. A mutation to disrupt the salt bridge results in promoting the cytoplasmic dissociation, thereby inducing integrin activation. b A conserved isoleucine at the α I domain C-terminal helix acts as a ratchet to stabilize the inactive conformation. A downward shift of the C-terminal helix is mediated by an interdomain interaction by the β I domain (also known as I-like domain). c Ca²⁺ binding site ADMIDAS in the β I domain favors the inactive low-affinity integrin headpiece conformation. A mutation to disrupt the Ca²⁺ binding site induces the constitutively active conformation by facilitating the conformational swing out of the hybrid domain