Journal
JOURNAL OF CELL SCIENCE
Volume 131, Issue 10, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.216754
Keywords
Laminin; Integrin; Electron microscopy; Conformational change
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT KAKENHI) [JP17H01420]
- Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Innovative Drug Discovery and Life Science Research (BINDS)] - Japan Agency for Medical Research and Development (AMED) [JP17am0101075, JP17am0101072]
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Structural analyses of beta 2 and beta 3 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 alpha v beta 3, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha 6 beta 4, and used negative-stain electron microscopy to examine their structures under various conditions. In contrast to av beta 3 integrin, which exhibited a severely bent conformation in low-affinity 5 mM Ca2+ conditions, all beta 1 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 alpha 6 beta 4 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.
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