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The identification and structural analysis of potential 14-3-3 interaction sites on the bone regulator protein Schnurri-3

DOI: 10.1107/S2053230X21006658 DOI Help

Authors: Lorenzo Soini (Eindhoven University of Technology; UCB Celltech) , Seppe Leysen (UCB Celltech) , Tom Crabbe (UCB Celltech) , Jeremy Davis (UCB Celltech) , Christian Ottmann (Eindhoven University of Technology)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology Communications , VOL 77 , PAGES 254 - 261

State: Published (Approved)
Published: August 2021

Open Access Open Access

Abstract: 14-3-3 proteins regulate many intracellular processes and their ability to bind in subtly different fashions to their numerous partner proteins provides attractive drug-targeting points for a range of diseases. Schnurri-3 is a suppressor of mouse bone formation and a candidate target for novel osteoporosis therapeutics, and thus it is of interest to determine whether it interacts with 14-3-3. In this work, potential 14-3-3 interaction sites on mammalian Schnurri-3 were identified by an in silico analysis of its protein sequence. Using fluorescence polarization, isothermal titration calorimetry and X-ray crystallography, it is shown that synthetic peptides containing either phosphorylated Thr869 or Ser542 can indeed interact with 14-3-3, with the latter capable of forming an interprotein disulfide bond with 14-3-3σ: a hitherto unreported phenomenon.

Journal Keywords: bone regulator protein; Schnurri-3; X-ray protein crystallography; phosphorylation; fluorescence polarization; disulfide bonds; 14-3-3 modes

Diamond Keywords: Bone

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Added On: 03/08/2021 09:29

Documents:
ag5041.pdf

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Non-Communicable Diseases Osteoporosis Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)