Dataset Information


On the contributing role of the transmembrane domain for subunit-specific sensitivity of integrin activation.

ABSTRACT: Integrins are α/β heterodimeric transmembrane adhesion receptors. Evidence exists that their transmembrane domain (TMD) separates upon activation. Subunit-specific differences in activation sensitivity of integrins were reported. However, whether sequence variations in the TMD lead to differential TMD association has remained elusive. Here, we show by molecular dynamics simulations and association free energy calculations on TMDs of integrin αIIbβ3, αvβ3, and α5β1 that αIIbβ3 TMD is most stably associated; this difference is related to interaction differences across the TMDs. The order of TMD association stability is paralleled by the basal activity of these integrins, which suggests that TMD differences can have a decisive effect on integrin conformational free energies. We also identified a specific order of clasp disintegration upon TMD dissociation, which suggests that the closed state of integrins may comprise several microstates. Our results provide unprecedented insights into a possibly contributing role of TMD towards subunit-specific sensitivity of integrin activation.


PROVIDER: S-EPMC5893634 | BioStudies | 2018-01-01


REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4132822 | BioStudies
2019-01-01 | S-EPMC6750892 | BioStudies
2015-01-01 | S-EPMC4281730 | BioStudies
2012-01-01 | S-EPMC3365499 | BioStudies
2009-01-01 | S-EPMC2680374 | BioStudies
2011-01-01 | S-EPMC3257387 | BioStudies
2017-01-01 | S-EPMC5532619 | BioStudies
1000-01-01 | S-EPMC5473239 | BioStudies
2014-01-01 | S-EPMC4345508 | BioStudies
2019-01-01 | S-EPMC6714448 | BioStudies