Ligand binding initiates single-molecule integrin conformational activation

• DOI: 10.1016/j.cell.2024.04.049
• Publication Date: 2024-05-20T14:32:24Z
• Authors: Jing Li; Myung Hyun Jo; Jiabin Yan; Taylor Hall; Joon Lee; Uriel López-Sánchez; Sophia Yan; Taekjip Ha; Timothy A. Springer
• Keywords: CD49c

Integrins link the extracellular environment to actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside inside is essential. Single-molecule fluorescence dynamics show that ligand binding bent-closed integrin conformation, which predominates on surfaces, followed within milliseconds by two concerted changes, leg extension headpiece opening, give high-affinity conformation. The extended-closed conformation not an intermediate but can be directly accessed from extended-open provides a pathway for dissociation. In contrast ligand, talin, links β-subunit cytoplasmic domain cytoskeleton, modestly stabilizes does induce or opening. Integrin activation thus initiated outside-in signaling inside-out signaling. Our results further imply talin insufficient tensile force transmission through ligand-integrin-talin-actin complex required.