Thursday, 6 February at 12h00, AD1-045/046
D-Life: The Importance of Proteome Homochirality Maintenance and Underlying Mechanisms
Homochirality is one of the key principles of life. Our proteins are composed of homochiral monomers, exclusively of L-amino acids (L-AAs), while D-amino acids (D-AAs) are thought to be non-proteinogenic. This is crucial because enzymes have stereo selective binding modes and therefore, do not cooperate with proteins partially or fully consist of D-amino acids.
Recent advances demonstrate that various stress conditions can lead to spontaneous emergence of D-AAs into proteins and to the loss-of-proteome enantiopurity, in other words to protein heterochirality. Furthermore, D-AAs have been detected in various aged human tissues and have been linked to several age-associated diseases. These indicate that the active maintenance of homochirality is required for homeostasis. While a few enzymes have been shown to control homochirality, the absence of specific tools and in vivo model system has precluded the identification of new chirality-regulating genes and no causal pathophysiological role for protein incorporated D-AAs have been established in vivo.
Recent work by Dr Banreti and her team shows that manipulating a key protein repair enzyme that contributes to the maintenance of protein homochirality, leads to the formation of melanotic tumours. The aim is to understand how heterochirality makes cells resistant to apoptosis, which is one of the key hallmarks of malfunctioning cells. The focus is on establishing a direct causal relationship between protein-bound D-amino acids and the pathophysiology of apoptotic cell death, using novel in vitro and in vivo chiral-specific cell death assays.
The team aims to identify a set of yet unknown chirality-regulating genes which are dedicated to protect proteome enantiopurity and to dissect the precise molecular mechanisms responsible for the maintenance of biological chirality. Interdisciplinary techniques are applied to routinely detect protein-bound D-AAs in vivo, using Drosophila as a powerful model system. Besides novel D-specific antibodies, the team has developed a high-throughput synchrotron radiation-based technology to study chiral-deficient live biological samples and apply a state-of-the-art chiral-specific analytical method to identify the extent of protein-bound amino acid isomerization.
In summary, this integrative approach will provide fresh insights into fundamental questions: how homochirality is actively maintained in live organisms and the mechanisms underlying the pathophysiological outcomes of the loss-of-enantiopurity.
About the presenter
Dr Agnes Banreti studied for her MSc degree in Cell, Developmental and Neurobiology. During her PhD she was working on autophagy at the Eotvos Lorand University, Budapest, Hungary and at The Institute of Developmental Biology Marseille, France. She then obtained an EMBO-Marie Curie European Commission COFUND grant and moved to The Institute of Cancer Research (ICR), London, UK to work as a postdoctoral fellow in the laboratory of Professor Pascal Meier. During her postdoctoral years, she studied the role of cell competition in cancer. Now an independent researcher at the Institute of Biology Valrose, Nice, France, she studies biological chirality.