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

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 osteo...

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Bibliographic Details
Published in:Acta crystallographica. Section F, Structural biology communications Vol. 77; no. 8; pp. 254 - 261
Main Authors: Soini, Lorenzo, Leysen, Seppe, Crabbe, Tom, Davis, Jeremy, Ottmann, Christian
Format: Journal Article
Language:English
Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England International Union of Crystallography 01.08.2021
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Subjects:
14-3-3 Proteins - chemistry
14-3-3 Proteins - genetics
14-3-3 Proteins - metabolism
14‐3‐3 modes
Amino Acid Sequence
Animals
Binding Sites - physiology
Biomedical materials
Bone growth
bone regulator protein
Calorimetry
Crystallography
Crystallography, X-Ray - methods
disulfide bonds
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Fluorescence
Fluorescence polarization
Humans
Mice
Osteogenesis
Osteogenesis - physiology
Osteoporosis
Peptides
phosphorylation
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins
Research Communications
Schnurri‐3
Structural analysis
Synthetic peptides
Therapeutic targets
Titration
Titration calorimetry
X‐ray protein crystallography
Zinc Fingers - physiology
Schnurri-3
disulfide bonds
bone regulator protein
fluorescence polarization
phosphorylation
14-3-3 modes
X-ray protein crystallography
ISSN:2053-230X, 2053-230X
Online Access:Get full text
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Summary: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. The structures of two peptide motifs of Schnurri‐3 in complex with 14‐3‐3 are reported.
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ISSN:2053-230X
2053-230X
DOI:10.1107/S2053230X21006658