Structural analyses of β2 and β3 integrins have revealed that they generally assume a compact bent conformation in the resting state and undergo a global conformational transition involving extension during upregulation of ligand affinity, collectively called the 'switchblade model'. This hypothesis, however, has not been extensively tested for other classes of integrins. We prepared a set of recombinant integrin ectodomain fragments including αvβ3, α2β1, α3β1, α5β1, α6β1 and α6β4, and used negative-stain electron microscopy to examine their structures under various conditions. In contrast to αvβ3 integrin, which exhibited a severely bent conformation in low-affinity 5 mM Ca2+ conditions, all β1 integrin heterodimers displayed a mixed population of half-bent to fully extended conformations. Moreover, they did not undergo significant conformational change upon activation by Mn2+ Integrin α6β4 was even more resistant to conformational regulation, showing a completely extended structure regardless of the buffer conditions. These results suggest that the mechanisms of conformational regulation of integrins are more diverse and complex than previously thought, requiring more experimental scrutiny for each integrin subfamily member.
Keywords: Conformational change; Electron microscopy; Integrin; Laminin.
© 2018. Published by The Company of Biologists Ltd.