Just one small mistake in the protein structure—a misfold, a mutation, or even an incorrect amount of protein—can tip the balance from health to disease. Proteins are the body’s molecular machines, and when they malfunction, the consequences can be profound. Understanding these processes is crucial for addressing a myriad of health conditions.
The announcement comes as Nobel Prize-winner Max Perutz’s groundbreaking work on the 3D structure of haemoglobin continues to influence protein research. His discovery highlighted how even the tiniest change in structure can have life-or-death implications, as an affected protein may be rendered unable to perform its proper function in the body.
The Complexity of Protein Misfolding
Michele Vendruscolo, a researcher at Cambridge University’s Centre for Misfolding Diseases, focuses on what happens when proteins such as haemoglobin go rogue, leading to conditions like thalassaemia and sickle cell disease. “One should think of a protein as like a machine that carries out essential work in the body,” Vendruscolo explains. “Proteins are the workers that carry out disassembly and reassembly so that we can actually use the food that we eat.”
However, at times, especially with age or under stress, proteins are unable to achieve their native state and misfold. This misfolding can lead to a range of diseases. “The failure to fold is very common,” Vendruscolo notes. “There are, in fact, many diseases caused by protein misfolding and aggregation, such as Alzheimer’s disease, Parkinson’s disease, or even type 2 diabetes.”
Haemoglobin: A Case Study in Protein Function
Haemoglobin serves as a key example of how protein structure affects function. It is not only crucial for carrying oxygen throughout the body but also a well-studied protein that illustrates the importance of both protein quantity and conformation. Diseases like thalassaemia and sickle cell disease are directly related to these factors.
In thalassaemia, mutations decrease the production of haemoglobin, leading to insufficient protein levels. “It’s like if there are not enough workers, the production chain cannot actually function,” Vendruscolo explains. In contrast, sickle cell disease involves mutations that affect haemoglobin’s ability to function, despite adequate protein levels.
“The basic function of haemoglobin is to carry oxygen. It has to be able to change its shape in order to capture oxygen and release it,” Vendruscolo elaborates. “These mutations affect the ability to capture or release oxygen at the right time and in the right place.”
Implications for Treatment and Drug Discovery
Understanding the structure of proteins is pivotal for developing treatments. For sickle cell disease, one therapeutic strategy is to maintain haemoglobin in its monomeric state, reversing the self-association process that leads to dysfunction. This approach highlights the broader strategy of maintaining proteins in their functional state to combat various diseases.
Meanwhile, in the realm of neurodegenerative diseases like Alzheimer’s, the focus is on supporting the body’s protein homeostasis system. “We experience disease when, in some way, this protein homeostasis control starts to fail,” Vendruscolo points out. Enhancing this system can help maintain proteins in their functional state, offering a common thread in therapies aimed at correcting protein misalignment and aggregation.
Looking Forward: The Future of Protein Research
The move represents a significant step forward in understanding and treating diseases linked to protein misfolding. As research continues to uncover the complexities of protein structure and function, it opens new avenues for medical advancements and drug discovery. The ongoing challenge is to translate these scientific insights into effective therapies that can alleviate the burden of protein-related diseases worldwide.
As the scientific community delves deeper into the intricacies of protein behavior, the potential for breakthroughs in health and medicine grows. The future of protein research holds promise for not only understanding but also effectively managing diseases that affect millions globally.
