Towards the understanding of molecular motors and its relationship with local unfolding

• Published in: Quarterly reviews of biophysics 2024-05, Vol.57, p.e7, Article e7
• Main Authors: Alavi, Zahra, Casanova-Morales, Nathalie, Quiroga-Roger, Diego, Wilson, Christian A.M.
• Format: Article
• Language: English
• Subjects: Acceleration; Adenylate kinase; Animals; Antigens; Binding energy; Brownian motion; Catalysis; Catalysts; Chemical energy; Chemical reactions; Cracking (chemical engineering); Crystallography; Energy; Enzymes; Heat; Humans; Hypotheses; Kinases; Ligands; Molecular Motor Proteins - chemistry; Molecular Motor Proteins - metabolism; Molecular motors; NMR; Nuclear magnetic resonance; Nucleotides; Protein Unfolding; Proteins; Review; RNA polymerase; Strain energy; Substrates
• ISSN: 0033-5835; 1469-8994; 1469-8994
• DOI: 10.1017/S0033583524000052

Molecular motors are machines essential for life since they convert chemical energy into mechanical work. However, the precise mechanism by which nucleotide binding, catalysis, or release of products is coupled to the work performed by the molecular motor is still not entirely clear. This is due, in part, to a lack of understanding of the role of force in the mechanical–structural processes involved in enzyme catalysis. From a mechanical perspective, one promising hypothesis is the Haldane–Pauling hypothesis which considers the idea that part of the enzymatic catalysis is strain-induced. It suggests that enzymes cannot be efficient catalysts if they are fully complementary to the substrates. Instead, they must exert strain on the substrate upon binding, using enzyme-substrate energy interaction (binding energy) to accelerate the reaction rate. A novel idea suggests that during catalysis, significant strain energy is built up, which is then released by a local unfolding/refolding event known as ‘cracking’. Recent evidence has also shown that in catalytic reactions involving conformational changes, part of the heat released results in a center-of-mass acceleration of the enzyme, raising the possibility that the heat released by the reaction itself could affect the enzyme’s integrity. Thus, it has been suggested that this released heat could promote or be linked to the cracking seen in proteins such as adenylate kinase (AK). We propose that the energy released as a consequence of ligand binding/catalysis is associated with the local unfolding/refolding events (cracking), and that this energy is capable of driving the mechanical work.