Title:	Cryo-EM structure determination of SLC transporters in human health and disease
DNr:	Berzelius-2024-74
Project Type:	LiU Berzelius
Principal Investigator:	Ayaan Ali <ayaan.abdi.ali@gu.se>
Affiliation:	Göteborgs universitet
Duration:	2024-02-27 – 2024-09-01
Classification:	10601
Keywords:

Abstract

The solute carrier (SLC) superfamily is home to more than 400 transporters, of which a growing number have been implicated in Mendelian diseases (monogenic diseases) as mutations in substrate-specific transporters give rise to disease phenotypes. Zinc transporter 3 (ZnT-3) is part of the SLC30 family responsible for accumulating zinc into vesicle compartments in the cell. ZnT-3 has been shown through histochemical studies in rat and mice to accumulate zinc in primarily glutamatergic circuits in the hippocampus, the amygdala, and the cortex. Understanding the structural changes in ZnT-3 that give rise to cognitive impairment, febrile seizures, Alzheimer’s disease, and gendered schizophrenia is currently hampered by a lack of high-resolution structural images of the transporter. The objective of this project is to capture the structure of ZnT-3, as well as its clinically relevant mutations, at atomic resolution with single particle cryo-EM. Furthermore, analyse the large collection of micrographs using the Cryo-EM PReSTO package in Berzelius, primarily using Relion and CryoSparc software in that package, as well as the deep learning tool Topaz to refine particle picking in the dataset.