Protein-Ligand Interaction

Running head: BIOCHEMISTRY AND MOLECULAR BIOLOGY
Protein-Ligand Interaction
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BIOCHEMISTRY AND MOLECULAR BIOLOGY
Insulin is an anabolic hormone, peptide in nature, that is secreted from beta-cells of
islet of Langerhans of the pancreas. The Insulin Receptor is a transmembrane receptor
belonging to the tyrosine kinase superfamily, and can be of two types IGF1 and IGF 2
(Insulin Like Growth Factor). The interaction of insulin receptor (a protein) and insulin (a
ligand) will be discussed here (Tatulian, 2015).
Fig.1- Insulin araeceptor Isoforms (Source- Pollak, 2012).
Insulin as a ligand binds on two different subunits of the receptor IGF1 or IGF2,
crosslinking the receptors, activating the signalling cascade. The interaction of the ligand and
the receptor has a very important role to play in glucose homeostasis. In liver, the interaction
results in conversion of glucose to glycogen and in muscles and fat, the interaction helps in
glucose transport through GLUT4 transporter. Eventually, the blood glucose level is
controlled. This interaction helps in activation of the pathway via IRS proteins (Insulin
receptor substrate 1), and activating the P13K (Phosphatidylinositol 3 kinase) and the ERK
(Extracellular-signal-regulated kinase) or MAPK (Mitogen Activated Protein Kinase). The
insulin binds with the receptor inducing a conformational change that activates the adaptor
protein IRS. PI3K then phosphorylates and activates PIP2 (phosphatidylinositol 4,5
bisphosphate), that activates PIP3, and finally AKT (Protein kinase B). One protein PDK 1

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BIOCHEMISTRY AND MOLECULAR BIOLOGY
and the upper cascade activate AKT that enters cytoplasm to phosphorylate and inactivate
GSK3. Glycogen Synthase (enzyme of glycogen synthesis) is a substrate of GSK3. GSK3
binds with the enzyme inhibiting glycogen synthesis. But, inactivation of the same helps in
glycogen formation and storage in liver. The other pathway activated by the protein-ligand
interaction is MAPK- pathway (D’Oria et al., 2017).
Fig.2- Signalling Pathways of Insulin and IR (Source- D’ Oria et al., 2017)
The interaction between insulin and insulin receptor is a major player to maintain
blood glucose level, glycogen synthesis and fat storage. Apart from that, insulin is expressed
in Bcells, Tcells, and macrophages. During T-cell receptor activation, the interaction
increases to mediate T-Cell proliferation, which have immense role to play during
inflammatory responses and acute infections. Deficiency of insulin can cause diabetes type 2,
which results in disruption of above pathways (Voet, Voet & Pratt, 2016)