Abstract:
:We use super-resolution interferometric photoactivation and localization microscopy (iPALM) and a constrained photoactivatable fluorescent protein integrin fusion to measure the displacement of the head of integrin lymphocyte function-associated 1 (LFA-1) resulting from integrin conformational change on the cell surface. We demonstrate that the distance of the LFA-1 head increases substantially between basal and ligand-engaged conformations, which can only be explained at the molecular level by integrin extension. We further demonstrate that one class of integrin antagonist maintains the bent conformation, while another antagonist class induces extension. Our molecular scale measurements on cell-surface LFA-1 are in excellent agreement with distances derived from crystallographic and electron microscopy structures of bent and extended integrins. Our distance measurements are also in excellent agreement with a previous model of LFA-1 bound to ICAM-1 derived from the orientation of LFA-1 on the cell surface measured using fluorescence polarization microscopy.
journal_name
Cell Repjournal_title
Cell reportsauthors
Moore TI,Aaron J,Chew TL,Springer TAdoi
10.1016/j.celrep.2018.01.062subject
Has Abstractpub_date
2018-02-13 00:00:00pages
1903-1912issue
7issn
2211-1247pii
S2211-1247(18)30111-6journal_volume
22pub_type
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