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Exploring Calbindin-IMPase fusion proteins structure and activity

DOI: 10.1016/j.bbrep.2022.101266 DOI Help

Authors: James Noble (King's College London) , John R. Atack (University of Sussex)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemistry And Biophysics Reports , VOL 30

State: Published (Approved)
Published: July 2022
Diamond Proposal Number(s): 14891

Open Access Open Access

Abstract: Calbindin-D28k is a calcium binding protein that is highly expressed in the mammalian central nervous system. It has been reported that calbindin-D28k binds to and increases the activity of inositol Monophosphatase (IMPase). This is an enzyme that is involved in the homeostasis of the Inositol trisphosphate signalling cascade by catalysing the final dephosphorylation of inositol and has been implicated in the therapeutic mechanism of lithium treatment of bipolar disorder. Previously studies have shown that calbindin-D28k can increase IMPase activity by up to 250 hundred-fold. A preliminary in silico model was proposed for the interaction. Here, we aimed at exploring the shape and properties of the calbindin-IMPase complex to gain new insights on this biologically important interaction. We created several fusion constructs of calbindin-D28k and IMPase, connected by flexible amino acid linkers of different lengths and orientations to fuse the termini of the two proteins together. The resulting fusion proteins have activities 200%–400% higher the isolated wild-type IMPase. The constructs were characterized by small angle X-ray scattering to gain information on the overall shape of the complexes and validate the previous model. The fusion proteins form a V-shaped, elongated and less compact complex as compared to the model. Our results shed new light into this protein-protein interaction.

Journal Keywords: Inositol monophosphatase; Calbindin-D28K; Inositol; Fusion protein; Bipolar disorder; Autophagy; SAXS

Diamond Keywords: Bipolar Disorder

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: B21-High Throughput SAXS

Added On: 04/05/2022 10:19

Documents:
1-s2.0-S2405580822000668-main.pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Biochemistry Neurology Chemistry Biophysics Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)