Effects of the association of the αvβ8 lower legs on integrin ligand binding

• Published in: Journal of cellular biochemistry Vol. 122; no. 8; pp. 801 - 813
• Main Authors: Song, Guannan, Luo, Bing‐Hao
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.08.2021
• Subjects: Binding; Cell surface; conformation; Glycosylation; Horses; Integrin αvβ8; Integrins; Interfaces; Leg; ligand binding; Ligands; Mutants; signaling; structure
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.29912

Many integrins transmit signals through global conformational changes. However, it is unclear whether integrin αvβ8 adopts a similar mechanism during integrin activation and signaling on the cell surface. Here, we showed that disulfide‐bonded mutants, which prevented integrin αvβ8 lower leg dissociation, bound ligands with similar level as the wild‐type protein, suggesting that αvβ8 ligand binding did not require lower leg disassociation. We further showed that the N‐glycosylation mutant at the interface between the β I and hybrid domains did not affect ligand binding, suggesting that the αvβ8 open headpiece was not present on the cell surface. We proposed that αvβ8 integrin may adopt only one state, that is, the extended conformation with a closed headpiece. Our results showed that two lower legs retained heterodimeric interfaces, and this association might be important for stabilizing integrin in the extended conformation. Therefore, αvβ8 may not transmit bidirectional signals across the plasma membrane but instead may serve as an anchoring site with high affinity and high accessibility for extracellular ligands. In this study, we evaluated the role of integrin αvβ8 lower leg association in mediating ligand binding. Our findings suggested that two lower legs of αvβ8 retained heterodimeric interfaces upon the ligand binding. Moreover, we found that the αvβ8 open headpiece did not exist on the cell surface. Our findings suggested that αvβ8 integrin may adopt only one state (the extended conformation with a closed headpiece).