Naslov
Defining the aggregation-critical region of the schizophrenia-related protein TRIOBP-1

Autori
Maja Odorčić

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
Odjel za biotehnologiju

Mjesto
Rijeka

Datum
16.07

Godina
2019

Stranica
50

Mentor
Nicholas Bradshaw ; Rozi Andretić Waldowski

Ključne riječi
mental illness, protein aggregation, TRIOBP-1, schizophrenia

Sažetak
Schizophrenia, major depressive disorder and bipolar depressive disorder are categorized as chronic mental illnesses due to their lifelong and recurring nature. The complexity of their biological and environmental background has made it difficult to determine the causes of such disorders as well as developing successful treatment therapies. The recent discovery of several proteins found aggregating in brain samples taken from patients suffering from chronic mental illness indicates that disrupted proteostasis may be one of the mechanisms contributing to the development of these disorders. Trio and F-actin-binding protein 1 (TRIOBP-1) was one of the proteins found aggregating in brain tissue of schizophrenia patients. Further study of this protein suggested that its aggregation propensity relies on a 25-amino acids long “linker region” positioned in the central domain (amino acids, aa 324-348), in between the first two coiled- coils. Here, we used plasmid constructs containing the desired regions of TRIOBP-1 and over-expressed them in mammalian cells. We confirmed that the proposed linker region is responsible for the aggregation of TRIOBP-1 and refined it to an even shorter sequence. We narrowed it down to an 8-amino acid long sequence (aa 333-340), however, the following amino acids (aa 341-348) also retained some of the TRIOBP-1’s aggregation propensity. We propose that this refined aggregating region should be the focus of future research in understanding the molecular mechanisms of TRIOBP-1’s disrupted proteostasis, giving us insight into the pathology of chronic mental illness.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA