Shape and interactions of the building blocks of biomolecular architectures

• Main Author: Giubertoni, G.
• Format: Book
• Language: English
• Published: 2020
• Subjects: Antarctic; Antarc*
• Online Access: https://dare.uva.nl/personal/pure/en/publications/shape-and-interactions-of-the-building-blocks-of-biomolecular-architectures(cb1b6b35-743b-4e3e-8ee7-f71b5a607f4c).html; https://hdl.handle.net/11245.1/cb1b6b35-743b-4e3e-8ee7-f71b5a607f4c; https://pure.uva.nl/ws/files/51019758/Thesis.pdf; https://pure.uva.nl/ws/files/51019760/cover.jpg

What does an anti-freeze protein found in an Antarctic fish have in common with hyaluronan, a long polymer found in the human body, and with a simple acid molecule found in a bottle of vinegar? Anti-freeze glycol proteins (AFGP), hyaluronan, and carboxylic acid have a flexible structure in aqueous solutions at room temperature. I used a state-of-the-art spectroscopic technique to resolve these molecules' structural dynamics, two-dimensional infrared spectroscopy (2DIR). Thanks to the ability of 2DIR to determine angles between coupled molecular groups, undeniable proof of the existence of two distinct conformational isomers of –COOH groups, syn- and anti-, in bio-relevant conditions was found. We observed that syn- and anti-conformers exist in different molecules ranging from simple formic acid to complex peptides. We found that the relative fraction of anti- increases from 25% to 60% by switching from a hydrophilic to a hydrophobic environment. By combining 2DIR with multiple different techniques (rheology, single-molecule force spectroscopy, molecular simulations), we linked conformational changes in hyaluronan polymers to the different macroscopic properties displayed by hyaluronan hydrogels. For example, the liquid-to-gel transition to which hyaluronan solutions undergo at pH 2.5 is due to the formation of a hydrogen-bonded network, where specific interchain interactions act in between carboxyl and amide groups. We finally found that anti-freeze glycol proteins (AFGPs) adopt PPII structure when the temperature is lowered to the working temperature, showing the importance of a specific conformation for the anti-freezing activities of AFGP.