Integrin domain organization and conformational states. Two lower β leg conformations (one with a dashed line) are shown for the extended states because the lower β leg is highly flexible (Takagi et al., 2002), and these states can exist with the α and β TM domains either associated or separated (Zhu et al., 2007b). However, signal transmission through the membrane, both in the inside-out and outside-in directions, requires TM and cytoplasmic domain separation (Kim et al., 2003; Luo et al., 2004a; Zhu et al., 2007b).