Direct optical measuerement of intramolecular distances with angstrom precision

Authors

Sahl SJ, Matthias J, Inamdar K, Weber M, Khan TA, Brüser C, Jakobs S, Becker S, Griesinger C, Broichhagen J, Hell SW

Journal

Science

Citation

Science. 2024 Oct 11;386(6718):180-187.

Abstract

Optical investigations of nanometer distances between proteins, their subunits, or other biomolecules have been the exclusive prerogative of Förster resonance energy transfer (FRET) microscopy for decades. In this work, we show that MINFLUX fluorescence nanoscopy measures intramolecular distances down to 1 nanometer—and in planar projections down to 1 angstrom—directly, linearly, and with angstrom precision. Our method was validated by quantifying well-characterized 1- to 10-nanometer distances in polypeptides and proteins. Moreover, we visualized the orientations of immunoglobulin subunits, applied the method in human cells, and revealed specific configurations of a histidine kinase PAS domain dimer. Our results open the door for examining proximities and interactions by direct position measurements at the intramacromolecular scale.

DOI

10.1126/science.adj7368
 
Pubmed Link