Exploring Calbindin-IMPase Fusion Proteins Structure and Activity

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2022 May 11

PMID 35540435

Authors

James W Noble

John R Atack

Affiliations

Soon will be listed here.

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.

References

Hallcher L, Sherman W . The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Biol Chem. 1980; 255(22):10896-901. View

Berridge M, Downes C, Hanley M . Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J. 1982; 206(3):587-95. PMC: 1158627. DOI: 10.1042/bj2060587. View

ALLISON J, Stewart M . Reduced brain inositol in lithium-treated rats. Nat New Biol. 1971; 233(43):267-8. DOI: 10.1038/newbio233267a0. View

Chichili V, Kumar V, Sivaraman J . Linkers in the structural biology of protein-protein interactions. Protein Sci. 2012; 22(2):153-67. PMC: 3588912. DOI: 10.1002/pro.2206. View

MAJERUS P . Inositol phosphate biochemistry. Annu Rev Biochem. 1992; 61:225-50. DOI: 10.1146/annurev.bi.61.070192.001301. View

Hennecke J, Wiley D . Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and.... J Exp Med. 2002; 195(5):571-81. PMC: 2193773. DOI: 10.1084/jem.20011194. View

Noble J, Almalki R, Roe S, Wagner A, Duman R, Atack J . The X-ray structure of human calbindin-D28K: an improved model. Acta Crystallogr D Struct Biol. 2018; 74(Pt 10):1008-1014. PMC: 6173056. DOI: 10.1107/S2059798318011610. View

Criollo A, Maiuri M, Tasdemir E, Vitale I, Fiebig A, Andrews D . Regulation of autophagy by the inositol trisphosphate receptor. Cell Death Differ. 2007; 14(5):1029-39. DOI: 10.1038/sj.cdd.4402099. View

ALLISON J, Blisner M, Holland W, Hipps P, Sherman W . Increased brain myo-inositol 1-phosphate in lithium-treated rats. Biochem Biophys Res Commun. 1976; 71(2):664-70. DOI: 10.1016/0006-291x(76)90839-1. View

10.

Kraft L, Roe S, Gill R, Atack J . Co-crystallization of human inositol monophosphatase with the lithium mimetic L-690,330. Acta Crystallogr D Struct Biol. 2018; 74(Pt 10):973-978. DOI: 10.1107/S2059798318010380. View

11.

Furuichi T, Yoshikawa S, Miyawaki A, Wada K, Maeda N, Mikoshiba K . Primary structure and functional expression of the inositol 1,4,5-trisphosphate-binding protein P400. Nature. 1989; 342(6245):32-8. DOI: 10.1038/342032a0. View

12.

Levi I, Eskira Y, Eisenstein M, Gilon C, Hoffman A, Tal-Gan Y . Inhibition of inositol monophosphatase (IMPase) at the calbindin-D28k binding site: molecular and behavioral aspects. Eur Neuropsychopharmacol. 2013; 23(12):1806-15. DOI: 10.1016/j.euroneuro.2013.02.004. View

13.

Berggard T, Miron S, Onnerfjord P, Thulin E, Akerfeldt K, Enghild J . Calbindin D28k exhibits properties characteristic of a Ca2+ sensor. J Biol Chem. 2002; 277(19):16662-72. DOI: 10.1074/jbc.M200415200. View

14.

Yin Y, Li Y, Kerzic M, Martin R, Mariuzza R . Structure of a TCR with high affinity for self-antigen reveals basis for escape from negative selection. EMBO J. 2011; 30(6):1137-48. PMC: 3061028. DOI: 10.1038/emboj.2011.21. View

15.

Kojetin D, Venters R, Kordys D, Thompson R, Kumar R, Cavanagh J . Structure, binding interface and hydrophobic transitions of Ca2+-loaded calbindin-D(28K). Nat Struct Mol Biol. 2006; 13(7):641-7. DOI: 10.1038/nsmb1112. View

16.

Streb H, Irvine R, Berridge M, Schulz I . Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate. Nature. 1983; 306(5938):67-9. DOI: 10.1038/306067a0. View

17.

Harwood A . Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Mol Psychiatry. 2004; 10(1):117-26. DOI: 10.1038/sj.mp.4001618. View

18.

Sarkar S, Floto R, Berger Z, Imarisio S, Cordenier A, Pasco M . Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol. 2005; 170(7):1101-11. PMC: 2171537. DOI: 10.1083/jcb.200504035. View

19.

Newton A . Protein kinase C: structure, function, and regulation. J Biol Chem. 1995; 270(48):28495-8. DOI: 10.1074/jbc.270.48.28495. View

20.

Schmidt H, Schwaller B, Eilers J . Calbindin D28k targets myo-inositol monophosphatase in spines and dendrites of cerebellar Purkinje neurons. Proc Natl Acad Sci U S A. 2005; 102(16):5850-5. PMC: 556286. DOI: 10.1073/pnas.0407855102. View