Proteins that do not give up easily: Heat-stable & acid-stable proteins

By Muhammad Ahmad and Rana Salman Anjum

We know when cooking an egg we solidify it, this is caused by its proteins undergoing denaturation (loss of original structure) and coagulation (random joining) (Figure 1). You might know our stomachs also have an acidic environment (pH of 2) which denatures proteins present in our food. You might also know, that thermophiles (microbes that grow in temperature ranges of 45 °C – 110 °C) are made up of heat-stable proteins, and the lumen (central cavity) of our stomach contains a few acid-stable proteins.

Figure 1: Denaturation and aggregation/coagulation of a protein. (A) During denaturation, hydrogen bonds of the natured (original) state of a protein are broken, and the protein is converted into a denatured (unfolded) state. (B) When activation energy of denaturation is provided, natured state first converts into a high energy denatured state and then loses energy to convert into a low energy aggregated/coagulated state. Adapted from ” Thermal Stability of Proteins,” by X. He andJ. C. Bischof, 2006, Annals of the New York Academy of Sciences, 1066(1), p. 12-33. Copyright 2006 by the John Wiley and Sons. Adapted with permission.

However, what you may not know is that mesophiles (microbes that grow between 20 °C and 45 °C) possess heat-stable proteins. Escherichia coli, a mesophile that resides in guts of humans are unable to grow at 50 °C, but some proteins are still stable at 100 °C. More interestingly, these heat-stable proteins are also present in eukaryotes living at moderate temperatures, e.g. plants and even us (humans).

Although fever (core temperature of 38.3 °C or higher) disrupts structures and functions of our proteins, scientists have characterised heat-stable proteins from us that are stable at 100 °C (think about what happens to our bodies at 100 °C). These scientists also compared the thermal behaviour of these proteins with each other and with heat-stable proteins from thermophiles. Thus, they divided heat-stable proteins into 4 groups. Heat-stable proteins from thermophiles constituted 1 group, while heat-stable proteins from other organisms, including humans, made up the other 3 groups (Figure 2).

Figure 2: Most of the proteins are heat-labile proteins, which, at high temperatures, unfold (lose their structure) and precipitate (thus, become insoluble). However, heat-resistant/heat-stable proteins do not lose their solubility at high temperatures and are divided into 4 groups. Only Group IV contains heat-stable proteins from thermophiles (more precisely from hyperthermophiles). These proteins retain their original (native) structures at high temperatures. On the other hand, Groups I, II, & III contain heat-stable proteins from other organisms (such as mesophiles and eukaryotes living at moderate temperatures). These proteins are actually unfolded at high temperatures, but they have the full (Groups I & III) or partial (Group II) abilities to return to their original/soluble structures. Adapted from “Thermal Behavior of Proteins: Heat-Resistant Proteins and Their Heat-Induced Secondary Structural Changes,” by T. D. Kim et al., 2000, Biochemistry, 39, p. 14839-14846.

Out of the above 4 groups, one group (Group I in Figure 2) consists of very important heat-stable proteins called ‘intrinsically disordered proteins’ (proteins lacking any well-defined structure). These proteins are involved in many human disorders, particularly in neurodegenerative disorders. Parkinson’s disease, Alzheimer’s disease, Amyotrophic Lateral Sclerosis, and Down’s Syndrome are well-known examples of neurodegenerative disorders caused by misfolding of these proteins.

Furthermore, heat-stable proteins, especially those from thermophiles, are used in many applications requiring high temperatures. Heat-stable enzymes are used in research procedures (e.g. Polymerase Chain Reaction) and industrial processes (e.g. food processing and ethanol production) that require high temperatures. Additionally, heat shock proteins, a type of heat-stable protein, employ many ways to protect cells of all living organisms, from different types of stressful conditions.

Besides, compared to heat-stable proteins, acid-stable proteins have not been studied in as much detail. These proteins are present abundantly in acidophiles (microbes that can grow at pH < 3), but some of them are also present in mesophiles and eukaryotes (pepsin is a famous example in humans). Some heat-stable proteins, from thermophiles and other organisms, are even acid-stable as well (nonetheless, not all heat-stable proteins are acid-stable and vice versa). Major applications of acid-stable proteins/enzymes are in industrial processes, mainly those involving polymer degradation, that are carried out at low pH. Finally, there are not just heat-stable and acid-stable proteins, there are other types of resistant proteins as well. For example, some proteins are cold-stable and protease-resistant, and have evolved to remain stable under various kinds of extreme conditions. We are yet to fully realise the potential of all these proteins and the applications they might be used in.

Further reading:

Kim, T.D., Ryu, H.J., Cho, H.I., Yang, C.H. and Kim, J., 2000. Thermal behavior of proteins: heat-resistant proteins and their heat-induced secondary structural changes. Biochemistry, 39(48), pp.14839-14846.

Kwon, S., Jung, Y. and Lim, D., 2008. Proteomic analysis of heat-stable proteins in Escherichia coli. Bmb Rep, 41(2), pp.108-11.

About the authors:

Muhammad Ahmad

I recently graduated with Summa Cum Laude and Outstanding Student Awards, with BS Hons Biotechnology from Forman Christian College (a Chartered University), Pakistan. Earlier, I was selected, among 500 leading young scientists from all over the world, for the London International Youth Science Forum (2018). I also represented Pakistan in the International Biology Olympiad, Denmark (2015) and the International Volunteer Forum, Russia (2019). Currently, I am continuing my research on proteins and looking for a postgraduate research degree in neurosciences.

Facebook: muhammadahmad59

Rana Salman Anjum

I’m currently working as an Assistant Professor at Forman Christian College (a Chartered University) in Lahore, Pakistan. I’m keen to understand DNA repair, protein modification and cell cycle regulatory mechanisms using biochemical and biophysical approaches. I’m also interested in understanding the nature of proteins, especially heat / acid-stable proteins. Previously, I’ve worked with Dr Nick Robinson and Dr Luca Pellegrini at Cambridge University. More recently, I’m working on protein translation with Professor Fikrettin Sahin at Yeditepe University in Istanbul Turkey. In my free time I enjoy playing badminton and cricket.

ORCID: 0000-0002-7891-4553
Twitter: @RanaSalmanAnjum

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