Measuring Integrin Conformational Change on the Cell Surface with Super-Resolution Microscopy.

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 Rep

journal_title

Cell reports

authors

Moore TI,Aaron J,Chew TL,Springer TA

doi

10.1016/j.celrep.2018.01.062

subject

Has Abstract

pub_date

2018-02-13 00:00:00

pages

1903-1912

issue

7

issn

2211-1247

pii

S2211-1247(18)30111-6

journal_volume

22

pub_type

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