A recent study by researchers at the Indian Institute of Science, Education and Research (IISER) Kolkata, has resulted in the development of a novel molecular ‘switch’ that turns on in the presence of specific proteins.
Imagine inserting a USB flash drive, also called a pen drive, into its slot on a laptop. Haven’t we all struggled to get it right the first time in a few instances? When the pen drive eventually fits into its slot, a small light in it flashes on, indicating that everything is just fine. In biological systems, many important processes are set off only after a ‘precise binding’ of two molecules. However, how do we know of the binding? Wouldn’t it be much easier if a light flashes after every perfect binding, just like the pen drive?
In this study, the researchers have tried to do something similar! They have discovered a novel property of a class of compounds called dithiocarbamates (DTC), which act as a light switch whenever they bind to specific proteins called lectins.
The distribution of carbohydrates (sugars) on the cell surface is unique to every cell type. Lectins are proteins that play the role of connectors by binding to the surface sugars of two cells and aiding the exchange or transport of molecules. Several lectins like concanavalin (ConA) and wheat germ agglutinin (WGA), from both plants and animals, have been identified and studied. So, how do we study these cell-ambassadors? In comes the wonder compound, DTC.
DTCs are organic compounds whose solubility increases when bound with specific carbohydrates. The researchers of this study initially synthesised a mannose (a type of sugar) derivative of DTC to study its binding properties with the lectin, concanavalin. To their surprise, they discovered that DTC emitted light when it bound with concanavalin!
Some molecules absorb light and reflect it back with a different wavelength and colour, resulting in a phenomenon called fluorescence. Initially, the mannose-bound DTC did not show effects of fluorescence when the light was shone on it. However, when bound with concanavalin, it started emitting fluorescence, thereby signalling its bound state with concanavalin. Also, this effect increased with increasing concentrations of concanavalin saturating at 309 times the initial intensity of fluorescence. A similar result was observed when galactose (mannose but with a different arrangement of atoms) bound DTC reacted with the galactose-specific lectin, wheat germ agglutinin.
But what in lectins make the DTCs shine like a Christmas tree in December? Lectins, quite literally hate water (hydrophobic). When bound to DTC, they make the resulting compound hydrophobic too, creating a shield around it from the surrounding solution. The researchers propose this property may be the cause of the ‘turn on’ effect observed. This discovery would help to visualise the binding properties of lectins in a much easier way and thus open new doors to probe the salient role of lectins in biological systems.