한빛사논문
- 조회613
Jing Li,1,2,3,6 Myung Hyun Jo,1,2,6 Jiabin Yan,1,3 Taylor Hall,1,3 Joon Lee,1,3 Uriel Lo ´pez-Sa´nchez,1,3 Sophia Yan,1,4 Taekjip Ha,1,2,5,7,* and Timothy A. Springer 1,3,7,8,*
1Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
3Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
4Newton South High School, Newton, MA 02459, USA
5Howard Hughes Medical Institute, Boston, MA 02115, USA
6These authors contributed equally
7These authors contributed equally
8Lead contact
*Corresponding authors: correspondence to Taekjip Ha or Timothy A. Springer
Abstract
Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the bent-closed integrin conformation, which predominates on cell surfaces, is followed within milliseconds by two concerted changes, leg extension and headpiece opening, to give the high-affinity integrin conformation. The extended-closed integrin conformation is not an intermediate but can be directly accessed from the extended-open conformation and provides a pathway for ligand dissociation. In contrast to ligand, talin, which links the integrin β-subunit cytoplasmic domain to the actin cytoskeleton, modestly stabilizes but does not induce extension or opening. Integrin activation is thus initiated by outside-in signaling and followed by inside-out signaling. Our results further imply that talin binding is insufficient for inside-out integrin activation and that tensile force transmission through the ligand-integrin-talin-actin cytoskeleton complex is required.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-05-22)
- 국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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