Atypical structure and function of integrin αVβ8
Abstract
© 2020 Wiley Periodicals LLC Integrins are heterodimeric transmembrane proteins that play important roles in various biological processes. Most integrins serve as adhesion molecules and transmit bidirectional signaling across the cell membrane through global conformational changes from the bent closed to the extended open conformation. However, integrin β8 is distinctive in structure and function. Its cytoplasmic domain lacks the conserved protein-binding sequence, which is important in transmitting inside-out signals, suggesting that integrin β8 may have a different activation mechanism or lack such signaling. In addition, the ligand-binding or activating metal ion Mn2+ does not induce a global conformational change in integrin β8. It may have only one conformation, that is, an extended, closed conformation, but with high affinity for ligands under physiological conditions, and is, therefore, considered an atypical integrin member. The extended structure and high ligand-binding affinity of integrin αvβ8 make it ideal for encountering and binding ligands expressed on an opposing cell or in the extracellular matrix. In this review, we summarize the progress in integrin β8 research with a focus on its distinctive function and structure among integrin members.