Nowadays we all care about our proteins. Supermarket products proudly show the amount of proteins they contain and we are all somehow familiar with different protein powders. However, from the biochemical perspective, proteins are extremely complex: they have many properties and they can do a lot of different things. This complexity generates a variety of conflicting ways of arranging proteins into different taxonomies, but why is it so?
Let us start from the basics. Proteins are generally defined as macromolecules or organic compounds that are formed of one or more long chains of amino acids, folded into complex conformations. But their compositional structure and amino acids composition are not all that matters to proteins; their function or role is also important – that’s why we all care about them. This is reflected in the origin of the word itself. The term “protein” comes from the Ancient Greek “proteios”, meaning primary (or leading), and they are considered so because of their important role in many biological processes and cellular reactions. In other words, proteins have superpowers!
In textbooks, proteins are divided into two families depending on their function. There are fibrous proteins that have a role in making up tissues, such as keratin or elastin, and are globular proteins that have a physiological role, such as enzymes, cellular messengers and antibodies. These two classifications take into account the shape and conformation of proteins: fibrous proteins are usually long and narrow, while globular proteins are spherical. But this is not all there is: the two families also do different things.
Molecular biology and biochemistry have been spending a lot of time and resources to explain and understand protein functions and how such functions are related to the conformations of proteins. However, this task is not simple. If from a chemical perspective proteins are simply macromolecules, they are not so from a biological one: they are macromolecules doing something special. And the relation between their chemical structure and their function is not as simple as it might intuitively seem. To understand why, we need to keep in mind that proteins present four levels of structure. First, they have what is called a “primary structure”, which is just the linear sequence of amino acids. Second, proteins present a “secondary structure”, which refers to some stable geometrical patterns that are localised in some parts of the molecule. Third, proteins present a “tertiary and quaternary structure”, which gives the geometric and full structure of the protein. This final structure is also what is directly linked to the function of the protein and provides information about what the protein does.
However, the relation between the “primary structure” and the “tertiary and quaternary” structures is far from straightforward: different amino acids sequences can form similar quaternary structures (and thus have similar functions) and the same amino acids sequences can result in quite different structures (and thus have different functions). This affects how we classify proteins in taxonomies. From a physic-chemical perspective, we might be inclined to do so according to their chemical structure and primary amino acids chain. In this case, we can have either many proteins that play the same function or one unique protein that plays different functions. But structure is not all there is to proteins. From a biological perspective, what they do is more important than what they are. So if we follow a biological/functional approach, then we have one, two or three - or as many as the functions - different proteins.
The complexity of the relations between structure and function can be accounted for by some philosophical tools: namely the relations of multiple realisability and multiple determination. Multiple realisability refers to a phenomenon for which the same entity or property can be realised by different ones. For instance, the property of being an eye can be realised by different organs in different animals. Multiple determinability refers to the opposite phenomenon: when the same entity can be determined, or realise, different properties or other entities. For example, the same object can be used in different ways, realising different properties.
Multiple realisability and determination are also applicable to proteins. Let us consider a couple of examples. Haemoglobin is a kind of protein with the function to bind and release oxygen. This protein can be formed by two different amino acids chains that fold in similar ways so that they can both play the same function. The biochemical functions of haemoglobin can be considered an instance of multiple realisability: the function of binding and realising oxygen is realised by two distinct macromolecules that present some micro-structural differences. Another interesting example is the case of multifunctional proteins or “moon-light” proteins such as crystallins. Crystallins are structural proteins that are present in all vertebrates’ eye lenses, but they can also have an enzymatic role in digestive processes. This makes crystallins a case of multiple determination, as we have the same series of amino acids chain that can lead to very different functions.
These kinds of proteins and these phenomena generate the tension between the chemical and the biological approach to these molecules. This also affects how we organise our knowledge around proteins and how we can classify them. Biochemists and molecular biologists have been adopting both the chemical and the biological approach, describing structural proteins with many biological roles or biological proteins with multiple structures. But it seems that no scheme can perfectly capture both.
Conflicting taxonomies do not only have an impact on scientific practice, but they also challenge our understanding of what proteins are and which proteins really exist. This is so because taxonomic schemes are often taken to be informative about what exists: scientific kinds might be those categories “carving nature at the joint”. Accordingly, the variety of joints that the physic-chemical approach and the biological approach carve can give us a very “messy” or un-neat view of the world. While it remains a possibility that the world is actually “messy”, some other solutions can still be explored.
The options on the table are at least three. The first is to assume that somehow - in a way not yet fully understood- the functions of proteins can be explained in terms of their structure and as such structural classifications will be the ones conveying more information and capturing the real nature of these proteins. In the examples, we wouldn’t just have haemoglobin, but rather two different kinds of proteins that play a haemoglobin-like role. Or, in the case of crystallins, we have one single kind that plays multiple roles. The second is to focus on what proteins do at the biological level, disregarding chemical characterisations in favour of biological ones. In this case, there is one haemoglobin, realised by two different amino acids chains. But, in the case of crystallins, we would have two different proteins: one that operates in vision and one in digestion. The third is to just deem both classifications as valid, but discipline-dependent. The same objects can be characterised in terms of whatever properties are relevant to our practical purposes and scientific goal. This approach cannot inform us about which kinds of proteins actually exist.
It might also be that none of these options is optimal. The first two seem to be missing out on some of the complexities of proteins: we need both structure and functions to understand them. The third one does not seem particularly satisfactory either as it as does not explain the complexity, but just accepts it and decides pragmatically what has to be done. Also, it does not help us in understanding what exists or not.
What can we do then? The super-powers of proteins challenge our conventional ways of thinking about the macromolecules in biology. Perhaps what we need then is a new approach that brings together structural and functional characterisations.
Further readings
Bartol, Jordan. 2016. “Biochemical kinds”. British Journal for the Philosophy of Science 67: 531- 551.
Bellazzi, Francesca. 2022. “The emergence of the postgenomic gene”. European Journal for Philosophy of Science, 12, 17.
Havstad, Joyce C. 2016. “Proteins: tokens, types and taxa” in C. Kendig (ed.), Natural Kinds and Classification in Scientific Practice. New York: Routledge.
Havstad, Joyce C. 2018. “Messy Chemical Kinds”. British Journal for Philosophy of Science. 69: 719-743.
Slater, Matthew H. 2009. “Macromolecular pluralism”. Philosophy of Science}, 76: 851-863.
Tahko, Tuomas E. 2020. “Where do you get your protein? Or: biochemical realization”. British Journal for the Philosophy of Science 71 (3): 799-825.
Tahko, Tuomas E. 2021. Unity of Science. Cambridge Elements in Philosophy of Science, Cambridge University Press.
Tobin, Emma. 2010. “Microstructuralism and Macromolecules: The case of moonlighting proteins”. Foundations of Chemistry 12 (1):41-54.
* Francesca Bellazzi is a PhD researcher in the ERC Metascience Project “The Metaphysical Unity of Science” (grant agreement n. 771509) at the University of Bristol. In her research, she investigates biochemical natural kinds and the relations between chemistry and molecular biology.
** You can read Francesca's latest publication "The emergence of the postgenomic gene" here.