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 α_IIbβ₃, α_vβ₃, and α₅β₁ that α_IIbβ₃ 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 difference

SUBMITTER: Pagani G 

PROVIDER: S-EPMC5893634 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature