Into the Proteome-verse

Shining light into the dark side of biology

RUSHALI

Into the Proteome-verse

Dear readers,

As biology students, you would definitely be familiar with the concept of a protein, and how they make up most of all living beings, and how they are the building blocks of life. Proteins have diverse functions, they are involved in various cellular processes like signaling, transport, metabolism, growth, development, etc. They are ubiquitous across all living systems.

We also learn, as biology undergraduates that proteins have a primary structure determined by amino acids that make it up, and the forces between the amino acids of the primary structures determine the secondary ones, and many secondary structures bend and twist around each other in a thermodynamically favorable way to give rise to tertiary structures and these sometimes come together to form quaternary structures.

Illustration by Rushali

Structure leads to function.

Illustration by Rushali

An accepted principle of protein biology is that as long as the structure is intact, the function of the protein would also be intact. This Is believed to be essential for the maintenance of cellular function. Misfolding of proteins by stress, inflammation, environmental factors, etc. leads to diseases. The body has effective clearance mechanisms for the same, ensuring quality control of proteins.

But, is 'Structure leads to function' the absolute truth about proteins?

This is what we learn first, when we read about diseases, that protein structure is absolutely crucial for function.

How sure is biology about this principle?

Biology will always be filled with exceptions. It is what drives constant change in life, leading to resilience, evolution, and adaptability.

So, today dear readers, I would like to introduce you to the concept of “Unstructure” or “Disorder” that exists in protein biology, about which none of you would have learnt in high schools or even your undergraduate or postgraduate studies.

This field is relatively recent, as most scientists often ignored this concept because of their bias towards the principle of structure specifying protein function. However, with better techniques, and more evolved biophysical methods, scientists now are able to decode what they previously thought was “dark proteins” meaning “proteins that could not be understood on a structural basis”.

These proteins are dynamic, and cannot be understood structurally by conventional methods like x-ray crystallography, circular dichroism, etc. These proteins are constantly in motion, and do not have fixed structures of their own at any point of time, and were an enigma to most scientists.

Illustration by Rushali

Disorder can also lead to function!

Now nothing in biology, I feel exists without a reason. If we think there is no function to something that exists in nature, it just means we haven’t understood it yet. Disordered proteins were later found to have so many functions. They work in such varied ways too. Some of them gain their function when they come near another protein, some just form a cacophony of binding regions, some ensure a newer biophysical phenomenon to help compartmentalize cellular components, and some help in cellular signalling regulation. And scientists have only scratched the surface of the whole concept!

This, my young future biologists, is why having an open mind in the field of biology is extremely important. It was easy for scientists to dismiss for years that the dark proteome could be studied. However, when they opened their minds a little, they realized that they were just viewing the beginning of an era of disorder-function paradigm which could explain way more about the biological world than before.

Illustration by Rushali

Concepts that seem unimaginable or very hard to understand require out-of-the-box thinking.

I think this is what science is about…pushing your understanding to uncover the secrets nature holds, despite finding ourselves in dark alleys that seem scary and futile to explore, but unearths more and more wonders, if you find out new ways to explore them.

Illustration by Rushali

That is why science is beautiful.

Wishing you best and all the luck you'd need to discover more.

Rushali

Illustration by Rushali

Editorial Note

When Rushali argues that “If we think there is no function to something that exists in nature, it just means we haven’t understood it”, she is making explicit a very important assumption in biological reasoning. When making explanations of biological phenomena, most biologists operate with the assumption that biological structures exist to serve a specific telos or purpose, which involves serving survival or reproduction related functions. For instance the heart serves the function of pumping blood, which helps in survival of the organism. However, this does not necessarily mean that the heart exists for the sole purpose of serving that function. Often, we find young students making such explanations.

For more on teleological reasoning in biology, check out this resource:

The relationship between biological function and teleology: Implications for biology education

About Rushali

Rushali Kamath is a third-year PhD scholar at IIT Mandi. She loves her research which could be frustrating at times, working with worms and doodling in her free time. She adores travelling all across Himachal in her free time and experiencing nature.