Frizzled-5 published in eLife

Cornelius Gati
09 August 2020

BRILliant news! Our paper in collaboration with the Chris Garcia and Anthony Kossiakoff labs was just released in eLife Sciences Publications, Ltd. We present the monomeric apo(!) cryoEM structure of Frizzled5 (resolved part <40 kDa) by using a BRIL-fusion, Fab, Nb complex.

‘Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling.’.

We believe that this could be a general tool for small membrane protein targets. Our structure gives insights into the activation mechanism, which is initiated by binding of Wnt to the receptor. Various attempts to solve the Wnt/Fzd5 complex were unfortunately not ‘successful’.

Many congrats to everyone involved, first and foremost to my friend and colleague Naotaka Tsutsumi who lead the heroic effort of imaging such a small target.

The original description of this exciting Fab and Nb combination was recently published by the Kossiakoff lab member Somnath Mukherjee in Nature Communications: ‘Synthetic antibodies against BRIL as universal fiducial marks for single−particle cryoEM structure determination of membrane proteins.’.